EPA 560/11-80-018
INVESTIGATION OF SELECTED
POTENTIAL ENVIRONMENTAL CONTAMINANTS:
STY RENE, ETHYLBENZENE, AND RELATED COMPOUNDS
May 1980
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
SYRACUSE RESEARCH CORPORATION
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EPA 560/11-80-018 TR-80-569
INVESTIGATION OF SELECTED POTENTIAL
ENVIRONMENTAL CONTAMINANTS:
STYRENE, ETHYLBENZENE, AND RELATED COMPOUNDS
Joseph Santodonato
William M. Meylan
Leslie N. Davis
Philip H. Howard
Denise M. Orzel
Dennis A. Bogyo
May 1980
FINAL REPORT
Contract No. 68-01-3250
SRC No. 1279-07
Project Officer - Frank Letkiewicz
Prepared for:
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C.
Document is available to the public through the National
Technical Information Service, Springfield, Virginia 22151
-------
NOTICE
This report has been reviewed by the Office of Toxic Substances, EPA,
and approved for publication. Approval does not signify that the contents
necessarily reflect the views and policies of the Environmental Protection
Agency, nor does mention of trade names or commercial products constitute
endorsement or recommendation for use.
ii
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Table of Contents
Page
EXECUTIVE SUMMARY xiii
I. Physical and Chemical Data 1
A. Structure and Properties 1
1. Chemical Structure and Nomenclature 1
2. Mixtures 1
3. Physical Properties of the Pure Material 3
4. Properties of the Commercial Materials 6
5. Principal Contaminants of the Commercial Products 11
B. Chemical Reaction in the Environment 13
1. Photochemistry 14
2. Hydrolysis 15
3. Liquid-Phase Oxidation 16
4. Photochemical Smog Reaction 18
5. Miscellaneous Reactions 22
II. Environmental Exposure Factors 27
A. Production Aspects 27
1. Quantity Produced, Imported and Exported 27
2. Producers, Production Sites, and Major Distributors 30
3. Current Production Methods 36
a. Ethylbenzene 36
(1) Liquid-Phase Benzene Alkylation 36
(2) Alkar Vapor-Phase Benzene Alkylation 40
(3) Fractionation of Ethylbenzene from Mixed 43
Xylene Streams
(4) Extraction from Styrene Tars 45
b. Styrene 45
(1) Dehydrogenation of Ethylbenzene 46
(2) Co-Product with Propylene Oxide 49
c. a-Methylstyrene 49
(1) By-Product from Cumene-Phenol Process 49
(2) Dehydrogenation of Cumene 50
d. Divinylbenzene 50
iii
-------
Table of Contents (Cont'd)
4. Market Price and Trends 53
a. Ethylbenzene 53
b. Styrene 56
c. a-Methylstyrene 56
d. Divinylbenzene 57
5. Quantity Produced as Contaminant of Other Materials 57
a. Ethylbenzene and Styrene 57
b. a-Methylstyrene and Divinylbenzene 59
B. Use Aspects 59
1. Consumption and Use Data 59
a. Ethylbenzene 59
b. Styrene 60
(1) Polystyrene 60
(2) ABS Resins 65
(3) SAN Resins 65
(4) Styrene-Butadiene Copolymer Latexes 66
(5) Other Copolymers Over 50% Styrene 66
(6) SBR Elastomers 67
(7) Unsaturated Polyester Resins 67
(8) Miscellaneous Polymers Less Than 50% Styrene 68
(9) Other 68
c. a-Methylstyrene 69
d. Divinylbenzene 69
2. Use Sites 70
3. Application of Products Containing Contaminants 70
a. Ethylbenzene 70
b. Styrene 79
4. Projected or Proposed Uses 79
5. Alternatives to Use 79
C. Entry Into the Environment 80
1. Points of Entry 80
a. Production 80
b. Use 81
c. By-Product or Contaminant 81
d. Miscellaneous Disposal 82
e. Monomer Migration from Polystyrene 82
iv
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Table of Contents (Cont'd)
Page
2. Emission and Effluent Control Methods 83
3. Production in the Environment 84
a. Motor Vehicle Exhausts 84
b. Combustion Systems 84
c. Pyrolysis 86
d. Cigarette Smoke 86
e. Incineration 86
D. Analytical Methods 87
1. Sampling Techniques 87
2. Chromatographic Methods 93
3. Spectroscopic Methods 99
4. Electrochemical and Miscellaneous Methods 101
E. Monitoring 103
1. The Atmosphere 103
2. Water 108
3. Food and Other Ingested Materials 112
4. Industrial Products 114
5. Miscellaneous Monitoring 115
III. Health and Environmental Effects 116
A. Environmental Fate and Transport 116
1. Biodegradation 116
2. Chemical Degradation 118
3. Environmental Transport 118
B. Biological Effects 119
1. Toxicity and Clinical Studies in Man 119
a. Occupational Studies 119
(1) Biological Monitoring 119
(2) Effects on Worker Health 126
b. Epidemiologic Studies 135
c. Controlled Metabolic Studies in Humans 137
(1) Absorption and Excretion 137
(2) Physiologic Effects 143
d. Poisoning Incidents 144
-------
Table of Contents (Cont'd)
2. Effects on Non-Human Mammals 145
a. Absorption/Excretion Studies 145
b. Metabolism and Pharmacology 151
c. Acute Toxicity 156
(1) Oral Administration 156
(2) Vapor Inhalation 159
(3) Skin Contact 163
(4) Eye Contact 163
(5) Other Routes 163
d. Subchronic Toxicity 167
(1) Oral Administration 167
(2) Vapor Inhalation 169
(3) Skin Contact 178
(4) Parenteral Administration 178
e. Teratogenicity 178
f. Mutagenicity 182
g. Carcinogenicity 194
3. Effects on Other Vertebrates 198
a. Fish 198
4. Effects on Invertebrates 198
5. Effects on Plants 198
6. Effects on Microorganisms 202
7. Biochemical Studies 209
IV. Regulations and Standards 213
A. Current Regulations 213
1. Labelling Requirements 213
a. Styrene 213
b. a-Methylstyrene 213
c. Ethylbenzene 214
d. Divinylbenzene 214
2. Food Tolerances 214
VI
-------
Table of Contents (Cont'd)
3. Standards for Human Exposure
a. Styrene Monomer
b. a-Methylstyrene
c. Ethylbenzene
d. Divinylbenzene
4. NFPA Hazard Identification Code
B. Current Handling Practices
1. Special Handling in Use
a. Styrene
b. a-Methylstyrene
c. Ethylbenzene
d. Divinylbenzene
2. Storage and Transport Practices
a. Styrene
b. a-Methylstyrene and Divinylbenzene
c. Ethylbenzene
3. Accident Procedures
a. First Aid Procedures
(1) Styrene
b. Spill and Leak Procedures
(1) Styrene
(2) a-Methylstyrene
(3) Ethylbenzene
(4) Divinylbenzene
TECHNICAL SUMMARY
References
Page
215
215
215
216
216
216
217
217
217
217
218
218
219
219
220
220
221
221
221
221
221
222
222
222
223
235
vn
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List of Tables
Number Page
1 Structure and Nomenclature of Styrene and Related Compounds 2
2 Physical Properties of Chemically Pure Styrene Compounds 4
3 Sales Specifications, Ethylbenzene 7
4 Sales Specifications, Styrene 8
5 Sales Specifications, a-Methylstyrene 9
6 Typical Commercial Product Values, Divinylbenzene 10
7 Typical Chemical Analysis of Styrene Monomers 12
8 Carbon Balance for Toluene - NOx System 21
9 Miscellaneous Reactions of Styrene Monomers and Ethylbenzene 24
10 U.S. Production of Ethylbenzene, Styrene, ex-Methylstyrene, and 28
Divinylbenzene
11 Imports and Exports of Ethylbenzene, Styrene, and a-Methyl- 29
Styrene
12 Producers of Ethylbenzene, Styrene, a-Methylstyrene, and 31
Divinylbenzene
13 Major Distributors of Styrene, Ethylbenzene, a-Methylstyrene, 34
and Divinylbenzene
14 Market Prices of Ethylbenzene, Styrene, a-Methylstyrene, and 54
Divinylbenzene
15 Styrene Consumption by End-Use in 1975 and Estimates for 1980 61
16 Estimated Consumption of Styrene by Consumer and Industrial 62
Product End-Use Markets - 1974
17 Analysis of Various Grades of Polystyrene 64
18 Use Sites for Styrene and Divinylbenzene Monomer 71
19 Tradenames for Various Polymer Products 78
viii
-------
List of Tables (Cont'd)
Number Page
20 Representative Volume Compositions of Hydrocarbon Component 85
of Vehicular Emissions
21 Sampling Methods for Styrene Monomers and Ethylbenzene 94
22 Chromatographic Analytical Methods for Styrene Monomers and 100
Ethylbenzene
23 Styrene and Ethylbeznene Concentrations (ppm V/V) in California 105
Air Samples
24 Atmospheric Monitoring Data for Styrene and Ethylbenzene 107
25 Styrene Identified in Water 109
26 Ethylbenzene Identified in Water 110
27 Styrene and Ethylbenzene Monitored in Water 113
28 Pure Culture Metabolism of Ethylbenzene and a-Methylstyrene 117
29 Metabolite Levels in Urine of Workers Exposed to Styrene 121
30 Subjective Symptoms Among Workers Processing Reinforced 129
Polyesters
31 Retention, Biotransformation, and Elimination of Ethylbenzene 139
and Styrene and Their Metabolites in Man
32 Skin Absorption of Styrene and Ethylbenzene 142
14
33 Percent of Administered C Activity Recovered in 72 Hours 146
Following a Single Oral Dose of 50 or 500 mg/kg ^C-Styrene
34 Styrene Content in Rat Organs Following Inhalation and Dermal 150
Exposures
35 Experimental Acute Oral Toxicity of Styrene and Derivatives 158
36 Experimental Acute Inhalation Toxicity of Styrene and 160
Derivatives
37 Irritation and Injury to the Eyes of Rabbits Caused by Contact 164
with Undiluted Materials
ix
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List of Tables (Cont'd)
Number Page
38 Intraperitoneal LD-Q Values for Styrene and Styrene Oxide 165
in Rats
39 Summary of Repeated Oral Feeding of Styrene and Ethylbenzene 168
to Female Rats
40 Results of Repeated Vapor Inhalation Studies on Animals 170
Exposed to Styrene
41 Results of Repeated Vapor Inhalation Studies on Animals 172
Exposed to Ethylbenzene
42 Results of Repeated Vapor Inhalation Studies on Animals 173
Exposed to a-Methylstyrene
43 Experimental Subchronic Inhalation Exposure to Styrene, 174
a-Methylstyrene, and Ethylbenzene
44 Subchronic Effects of Styrene Administered by Injection to 179
Experimental Animals
45 Mutagenicity of Styrene and Its Metabolites for Salmonella 183
46
47
48
49
50
typhimurium
Mutagenicity of Styrene Oxide to Salmonella typhimurium
Mutagenicity of Styrene to Salmonella typhimurium
Lack of Reversion of S. typhimurium TA1535 by Styrene in the
Presence of Different Amounts of Fortified Liver Homogenates
from Arochlor 1254-pretreated Rats and Hamsters
Forward Mutations (ade Mutants) Induced in Yeast S. Pombe
(Px Strain)
Forward Mutations (azg Mutants) Induced in Chinese Hamster
184
185
186
189
190
Cells (V?9 Strain)
51 Mutagenicity Test with Host-Mediated Assay (Mice): Gene 191
Conversion (S. Cerevisiae, D, Strain)
52 Mutagenicity Test with Host-Mediated Assay (Mice): Forward 192
Mutation (S. Pombe; ade Mutants; PI Strain)
-------
List of Tables (Cont'd)
Number Page
53 Effect of Modifiers of Microsomal Enzymes on 3-MC-Mediated 197
Transformation and Cytotoxicity in 10T1/2C18 Cells
54 Median Tolerance Limits for Styrene and Ethylbenzene Obtained 199
with the Moving Average-Angle and Graphical Interpolation
Methods
55 Comparison of Acute Toxicity of Petrochemicals to Different 200
Species of Fish
56 Significance of Difference Between Estimated 96-Hr TL Values 201
in Soft Water for Different Species m
57 Vitality and Growth of Algae in Water with Addition of Styrene 203
58 Vitality and Growth of Algae in Water with Addition of 204
Alpha-Methylstyrene
59 Growth and Changes in Pigmentation of Molds on Sabouraud-agar 205
with Addition of Styrene
60 Growth and Changes in Pigmentation of Molds on Sabouraud-agar 206
with Addition of ot-Methylstyrene
61 Growth of Streptomycetes on Mineral Agar with Addition of 207
Styrene
62 Growth of Streptomycetes on Mineral Agar with Addition of 208
o-Methylstyrene
xi
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List of Figures
Number Page
1 Ultraviolet Absorption Spectra of Styrene 5
2 Geographical Location of Production Sites for Ethylbenzene, 35
Styrene, Divinylbenzene, and a-Methylstyrene
3 Ethylbenzene Manufacture Via Benzene Alkylation (Ethylene) 37
4 Alkar Ethylbenzene Process 42
5 Ethylbenzene Via Mixed Xylene Fractionation 44
6 Styrene Production Via Ethylbenzene Dehydrogenation 47
7 Finishing Distillations Used in the Manufacture of Commercial 52
Divinylbenzene Monomer
8 Ethylbenzene Production by Year 55
9 Bead-Packed Absorber for Absorbing Styrene Monomer from Air 89
10 Design of Charcoal Filter and Filter Holder Containing Two 91
Charcoal Filters in Series
11 Glass Apparatus Allowing Continuous Extraction of Charcoal 92
Filters Using a Very Low Volume of Solvent
12 Possible Pathways for Metabolism of Styrene in Mammals 152
13 Probable Metabolic Pathways in the Biotransformation of 157
Ethylbenzene
XII
-------
EXECUTIVE SUMMARY
Four commercially related chemicals have been considered in this review:
ethylbenzene, styrene, a-methylstyrene, and divinylbenzene. Both ethylbenzene
and styrene are each produced in 6-7 billion pounds annually; ethylbenzene
from ethylene and benzene and styrene from ethylbenzene. Styrene is used in
the production of polystyrene and other resins, elastomers, and rubbers.
Although these production volumes are extremely high and may result in signi-
ficant losses to the environment, there are other commercial sources of ethyl-
benzene and styrene which may be equally as large. There are approximately
10 billion pounds of ethylbenzene found per year in catalytic reformate which
is blended into gasoline. Fyrolysis gasoline, which is formed during the
cracking of petroleum to form ethylene, provides about 57-96 million pounds of
ethylbenzene and 228-342 million pounds of styrene annually. Other possible
sources of ethylbenzene and styrene include residues in polystyrene (about
3.2 million pounds of styrene and 1.9 million pounds of ethylbenzene annually),
ethylbenzene from motor vehicle exhaust (280 millions pounds annually), tobacco
smoke (both styrene and ethylbenzene), and other conbustion and pyrolysis
processes. a-Methylstyrene and divinylbenzene are produced in much smaller
quantities (61.4 and 3.4 million pounds per year, respectively) and are used
as copolymers for styrene or other monomers. Styrene oxide, a commercial
chemical that has not been treated in great detail in this review, is produced
in 2 million pounds annually. This small production volume is significant
because this styrene metabolite is mutagenic and possibly carcinogenic.
Both ethylbenzene and styrene have been detected in air and water samples.
In water, concentration data are not available. Concentrations in urban air
xiii
-------
are around 0.2 to 5 ppb. In air, ethylbenzene appears to be about as stable
as toluene, while the styrenes are very reactive. In smog chamber studies,
ct-methylstyrene was ranked as one of the most reactive chemicals and styrene
was considered to be more reactive than most of the reactive olefins. Avail-
able aqueous biodegradability studies suggest that styrene and ethylbenzene
can be metabolized by microorganisms. From the physical properties, it appears
that bioconcentration in biological organisms is unlikely and evaporation from
soil and water should be relatively rapid.
In occupational situations, human exposure to styrene, ethylbenzene, or
a-methylstyrene is often associated with adverse health effects. Numerous
studies have been conducted to characterize the toxic potential of styrene,
whereas the toxicology of ethylbenzene and a-methylstyrene is less clearly
understood. Nevertheless, all three chemicals appear to produce the same
qualitative symptoms in humans who are acutely exposed, including irritation
of the mucous membranes and narcosis at high exposure levels. Among workers
chronically exposed to styrene, neurotoxicity involving both the central
nervous system and the peripheral nerves has been noted. Detailed studies
have not been conducted to characterize the effects of chronic exposure to
ethylbenzene, divinylbenzene, or a-methylstyrene in humans.
Concern has recently developed over reports linking occupational exposure
to styrene with an excess incidence of leukemia and lymphoma. This concern is
compounded by the recent demonstration of chromosome abnormalities in a group
of styrene workers. Thus far, however, sufficient confirmatory evidence has
not been obtained to either establish a direct cause-and-effect relationship
or to determine levels and duration of exposure required to produce such effects.
xiv
-------
A study conducted with rats has also indicated that styrene may be car-
cinogenic. In addition, styrene has produced mutations in bacterial cells in
the presence of a drug-metabolizing enzyme system. Most investigators believe
that the potential carcinogenicity/mutagenicity of styrene is due to the
metabolic formation of a reactive epoxide intermediate, styrene oxide, in the
body. However, it is not clear whether normal detoxification mechanisms in
the body are capable of removing certain minimum amounts of styrene oxide
before physiologic harm may occur. It is not likely that ethylbenzene is
metabolized via an epoxide intermediate, and thus its potential as a carcino-
gen /mutagen is doubtful, although little testing has been conducted. However,
ethylbenzene can produce a degeneration of reproductive cells in the testes
of both rabbits and monkeys.
In tests with several species of fish, ethylbenzene and styrene produced
varying numbers of deaths with acute exposures at concentrations greater than
25 mg/£. Neither compound appeared to have potential for cumulative toxicity.
The effects of ct-methylstyrene on most lower animals have never been studied.
It is not known whether adverse health or ecological effects may result
from present environmental levels of styrene, ethylbenzene, or a-methylstyrene.
Any effects on human health which may occur will almost certainly be less pro-
nounced than those observed in occupational situations. However, since the
carcinogenicity/mutagenicity of these chemicals is still unresolved, a true
risk assessment cannot be presently made. From the data which are now avail-
able there is no reason to believe that the general population is being
excessively exposed, or that lower animals and food-chain organisms are being
adversely affected. However, numerous data gaps must be filled before a final
evaluation can be presented.
xv
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I. Physical and Chemical Data
A. Structure and Properties
1. Chemical Structure and Nomenclature
The four compounds which are the subject of this review are
derivatives of benzene with short chain alkyl or alkenyl functional groups.
Table 1 shows the molecular structure of these compounds and gives their
common names, standard chemical nomenclature, and less common synonyms which
have appeared from time to time in the literature.
Aside from the superficial structural similarities of their
molecules, the compounds in this group of four are related to one another in
their respective roles in the manufacture of polystyrene plastics: ethylbenzene
as the precursor of styrene, and a-methylstyrene and divinylbenzene as copoly-
mers with styrene. The names just used for the latter three compounds, although
not standard chemical names, have become thoroughly entrenched through common
usage and are retained in this review.
o-Methylstyrene should be distinguished from methylstyrene
(methylethenylbenzene). Methylstyrene (not considered in this review) is used
as a copolymer with styrene and has the following structure:
HC==CH,
2. Mixtures
Divinylbenzene is manufactured by the dehydrogenation of mixed
isomers of diethylbenzene. Commercial divinylbenzene therefore consists
-------
Table 1. Structure and Nomenclature of Styrene and Related Compounds
Compound
Common Name
Standard Chemical Name
(Chemical Abstracts Nomenclature) Synonyms
HC=CH,
CH_C=CH
Ethylbenzene
Styrene
a-Methylstyrene
Ethylbenzene
Ethenylbenzene
1-Methylethenylbenzene
Phenylethene
Cinnamene
Cinnamol
Phenylethylene
Styrol
Vinyl benzene
Isopropenylbenzene
2-Phenylpropene
CH=CIL
Divinylbenzene
Diethenylbenzene
-------
principally of diluted mixtures of m- and p_-divinylbenzene (Coulter and Kehde,
1970). For the commercial purposes for which this mixture is usually employed,
it is not .necessary to separate the isomers.
Dow Chemical Company USA (personal communication, 1977) sells
divinyl benzene as a mixture of divinyl and ethylvinylbenzene isomers with a
small amount of diethylbenzene also included in the mixture (see Table 6).
Pure divinylbenzene (and pure isomeric mixtures of divinylbenzenes) are un-
stable with respect to polymerization to the extent that it is not practical
to market them commercially.
3. Physical Properties of the Pure Material
The physical properties of the styrene compounds are summarized
in Table 2. Styrene is a colorless, transparent, mobile liquid with a sweet,
pleasant, characteristic odor (Boundy and Boyer, 1952). It readily undergoes
aerial oxidation, producing aldehydes and ketones which impart a sharp, dis-
agreeable odor to the styrene. Humans are capable of detecting a minimum
-4
identifiable odor of styrene at concentrations on the order of 3.4 x 10 mg
of 99.6% styrene per liter of air (Smith and Hochstettler, 1969).
For practical chemical purposes styrene is insoluble in water,
but miscible in all proportions with a large number of commercial organic
solvents such as acetone, benzene, carbon tetrachloride, methanol, ethanol,
and carbon disulfide (NSC, 1971).
Styrene exhibits a strong, nearly continuous absorption of
ultraviolet radiation in the range from 220 nm to 300 nm (see Figure 1). Above
300 nm the ultraviolet absorption of styrene is negligible. Consequently,
styrene is not likely to be photochemically decomposed by direct adsorption of
-------
Table 2. Physical Properties of Chemically Pure Styrene Compounds
Molecular Weight
Color
Boiling Point, 760 torr
Freezing Point, °C
Density (gm/ml) @20°C
Vapor Pressure, torr
Viscosity (cps) @20°C
Solubility in H20, wt.%
Ethylbenzene
106.17
colorless
136.186°C
-94.975
0.86702
38.60 @20°C
0.02f
a
Styrene
104 . 14
colorless
145. 2°C
-30.628
0.9019
4.53 @20°C
0.730 @20°C
0.029 @20°Ce
o
Divinylbenzene
130.08
colorless
199. 5°C
-66.90
0.9289
1.53 @40°C
1.09
0.005 @25°Cb>c
Q
ot-Methylstyrene
118 . 18
colorless
165.38°C
-23.21
0.9106b
1.9 @20°C
0.940
0.056
Boundy and Boyer, 1952
^Coulter e£ al. , 1969
"refers to isomeric mixtures
, 1970
1971
Union Carbide Co.
-------
Wave Number in cm
,-1
50C
1.00
.80
.60
.40
.20
* -00'-
M
Q
8
I 3
1.00
.80
.60
.40
20
00
00 46000 42000 40(
i i i I . , , 1
XX
(
x
X"
.0005
/
%
)00 38000 36000 34000
I.I. 1
N
N
\
\
\
V
\
A
\
\
\
\0.0
^^
010%
!000 2100 2200 2300 2400 2500 2600 2700
Wave Length in Angstrom Units
Wave Number in cm~ 1
4000 32000 30000 28000 26000 24000 23000
1 i i i 1 i i i 1 . . . 1 i . 1 . i 1 . 1
T
1
I
^
s.
0 10
)7%
^
r\
\
2800
|
1.0101
\J
%
K
\
\
2900
"
3000
COMPOUND
STYRENE
SOURCE AND PURITY
THE DOW CHEMICAL CO
99 89%
STATE
TEMPERATURE
CELL LENGTH
SOLVENT
CONCENTRATION
SLIT WIDTH
INSTRUMENT
Solution
20° C
1 cm
Iso — OcunB
0005- 100
03-2 OMr
Bcckman
LABORATORY
THE DOW CHEMICAL CO
3000 3200 3400 3600 3800 4000 4200
Wave Length in Angstrom Units
4400
Figure 1. Ultraviolet Absorption Spectra of Styrene (Boundy and Boyer, 1952)
-------
sunlight at the surface of the earth since sunlight contains wavelengths that
are above 300 nm.
Pure monomeric a-methylstyrene is a colorless liquid (Boundy
and Boyer, 1952). Its physical and chemical properties are similar to those
of styrene, although it does not undergo polymerization as readily. Divinyl-
benzene and ethylbenzene likewise are colorless liquids, the former resembling
styrene in its properties, and the latter resembling toluene and the xylenes
(Cier, 1970). Divinylbenzenes are considerably less stable than styrene with
respect to polymerization (Dow Chemical, 1967). Ethylbenzene has a saturated
alkyl chain and does not undergo polymerization at all.
Although styrene type monomers and ethylbenzene are insoluble
in water from a pratical chemical point of view, their solubility is sufficient
to consider natural waterways a possible means of transport for these compounds
in the environment. In general, the solubility of alkylbenzenes is a function
of both the nature of the substituent chain and the positions of the substi-
tuents, if there is more than one (Sutton and Calder, 1975). On the basis of
solubility studies of alkyl benzenes in distilled water and seawater (Sutton
and Calder, 1975), it is likely that the styrene type monomers are all approxi-
mately 30% less soluble in seawater than distilled water. For example, ethyl-
benzene dissolves up to 161 ppm at 25°C in distilled water, but only 111 ppm
at 25°C in seawater.
4. Properties of the Commercial Materials
Typical sales specifications for commercial styrene compounds
are listed in Tables 3-6. These properties are very close to those of the
highest purity grade available, except for divinylbenzene which is sold and
-------
Table 3. Sales Specifications, Ethylbenzene
Union Carbide Corp. Monsanto Co.
Specific Gravity @20/20°C 0.8676 to 0.8684
Purity, % by wt., min. 99.5 99.5
Benzene, % by wt., max. 0.3
Diethylbenzene, % by wt., max. 0.2 0.010
Free Acid 0.005% by wt., max.,
as acetic acid
Color (Pt-Co) 15
Suspended Matter Substantially free
Toluene, % by wt., max. 0.2
Xylenes, % by wt., max. 0.11
Cumene, % by wt., max. 0.05
Sulfur, ppm, max. 10
Chlorides, ppm, max. 5
Bunion Carbide Product Information Sheet, F-41645 (1969)
Monsanto Product Data Sheet (1974)
-------
Table 4. Sales Specifications, Styrene
oo
Purity (wt. %) , min.
Color, APHA Pt-Co, max.
Polymer (ppm), max.
Sulfur (ppm), max. as sulfur
Chlorides (ppm), max. as chlorine
Peroxides (ppm), max. as H_0,,
Aldehydes (ppm), max. as benzaldehyde
Suspended Matter
Inhibitor (ppm), t-butyl catechol
Specific Gravity, 20/20°C
Amoco Chemicals Corp .
99.60
10
10
25
50
100
200
nil
12, min.
0.9070 - 0.9080
Cosden Oil and Chemical Co.
99.6
10
10
30
100
200
10 - 15
Monsanto Co.
99.5
10
15
30
100
100
200
10 - 15
Amoco Technical Data Sheet (1976)
'Cosden Oil and Chemical Co. Styrene Monomer 996 Data Sheet (1975)
"Monsanto Polymers and Petrochemicals Co. Data Sheet (1972)
-------
Table 5. Sales Specifications, a-Methylstyrene
Clark Chemical Corp.3 Skelly Oil Company
USS Chemicals
Purity, % min.
Phenol, % max.
Cumene, % max.
Butylbenzene, % max.
Acetone, % max.
Color (APHA), max.
94.0
0.1
2
2
3
150
90.0 (92.3 typ.)
0.2 (typ.)
4.3 (typ.)
0.7 (typ.)
98.5
i n
Residue, 7, typ.
Polymer (ppm), max.
Specific Gravity 25/25°C
Refractive Index (25°C)
Inhibitor Content, ppm
2.5
10
0.9030 - 0.9085
1.5340 - 1.5370
10 - 20
Clark Chemical Corporation Technical Data Sheet (1975)
Skelly Oil Co., data sheet for extracted AMS (crude product stream)
:USS Chemicals Product Specification Sheet (1973)
-------
Table 6. Typical Commercial Product Values, Divinylbenzene
(Dow Chemical USA Material Safety Data Sheet,
Divinylbenzene, 1977)
Divinylbenzenes (meta and para) 50 - 60%
Ethylvinylbenzene and diethylbenzene 40 - 50%
Boiling Point 383°F
Water Solubility 0.0052% @25°C
% Volatiles by volume 100
Appearance Pale straw liquid
Odor Disagreeable
10
-------
used commercially as a mixture of the m- and p_-isomers of divinyl and ethyl-
vinyl benzenes (see Table 6). It is important that commercial grade styrene
monomers be of high purity to assure predictable properties in the polymeriza-
tion products which are the nearly exclusive end products of the commercial
use of these compounds (except for ethylbenzene which is used almost exclusively
to make styrene).
Commercial grade styrene monomers all contain a polymerization
inhibitor such as £-butylcatechol (TBC). The concentration of the inhibitor
varies, depending on the ease of polymerization of the monomer. Divinylbenzene
may be sold with 1000 ppm TBC, a-methylstyrene with 10 ppm (Dow Chemical, 1967).
Most manufacturers are willing to vary the inhibitor content of the product
(usually by increasing it) according to the needs of the customer.
5. Principal Contaminants of the Commercial Products
As mentioned above, impurities in styrene monomers can adversely
affect the properties of the polymers. Manufacturers are therefore careful to
control the kind and quantity of impurities in commercial styrene chemicals
and practically all commercial production of styrene chemicals come close to
meeting reagent grade standards of chemical purity.
The sales specifications for ethylbenzene of the Charter Chemical
Company, Houston, Texas, indicate the typical purity (99.0 to 99.2%) and
impurities to be found in commercial grade ethylbenzene. The primary impuri-
ties are alkanes (paraffins) (typically, 0.5%), m- and p_-xylenes (typically,
0.3%) and toluene (typically. 0.1%).
Typical chemical analyses of styrene, a-methylstyrene, and divinyl-
benzene are shown in Table 7. TBC is listed as an impurity in this table, but
11
-------
Table 7. Typical Chemical Analysis of Styrene Monomers (Dow Chemical, 1967)
Purity %
Polymer ppm
Phenyl Acetylene ppm
Aldehydes as CHO ppm
Peroxides as HO ppm
Chlorides as CK ppm
Sulfur as S ppm
TBC ppm
Beta-Methylstyrene %
Isopropylbenzene %
meta Vinyltoluene %
para Vinyltoluene %
Total Divinylbenzene %
meta Divinylbenzene %
para Divinylbenzene %
Total Ethylvinylbenzene 7,
meta Ethylvinylbenzene %
para Ethylvinylbenzene %
Styrene a-Methylstyrene Vinyltoluene
Divinylbenzene
99.6 99.3 99.6
none none none
<5 58
10 10 10
53 5
10 5
10
12 15 12
5
40
5
230
1000
0.5
0.2
60
40
55.0
36.4
18.6
48.0
25.0
13.0
12
-------
it is, of course, added intentionally as a polymerization inhibitor. It
counteracts the effects of peroxides, which are good polymerization catalysts
and may account for minor variations in polymerization rates observed for
different batches of styrene (Dow Chemical, 1967). Aldehydes in the styrene
monomers tend to promote attack on metals such as copper. Elemental sulfur
reduces the molecular weight of the polymer product and catalyzes the photo-
chemical decomposition of the polymer (Dow Chemical, 1967). Unreacted ethyl-
benzene may also be present in styrene monomer, although it is not listed in
Table 7. In concentrations larger than 0.5% ethylbenzene has an appreciable
effect in reducing the molecular weight of polymerized styrene. Because it
cannot become part of the polymer chain, any residual ethylbenzene in the
polymer tends to evaporate, producing undesirable physical blemishes (Dow
Chemical, 1967).
Hannah et_ al. (1967) used gas chromatography to determine impur-
ities in four commercial samples of 55 to 60% divinylbenzene solution. In
addition to about a dozen unidentified compounds, the following were found in
one or more of the samples: benzene, toluene, ethylbenzene, cumene, ethyl-
toluene, styrene, a-raethylstyrene, m and p_-diethylbenzene, vinyltoluene, m and
£-ethylvinylbenzene, napthalene, and 1,2-dihydronapthalene.
B. Chemical Reaction in the Environment
The environmental chemistry of ethylbenzene, styrene or analogous
vinyl benzenes has not been definitively studied. Their study has mostly been
confined to research of importance to styrene polymerization and a few general
works. The only relevant publications are limited to smog chamber studies to
evaluate and rank the relative reactivity of various hydrocarbons (Levy, 1973).
13
-------
To evaluate environmental chemistry this report has drawn heavily upon mechan-
istic studies of analogous hydrocarbons as well as upon the known reactions of
the specific hydrocarbons under study. The discussion includes information
published in the classic treatise on styrene chemistry (Boundy and Boyer, 1952).
To facilitate discussion, the environmental chemistry is separated into
four parts: (a) photochemistry, (b) hydrolysis, (c) liquid phase oxidation,
and (d) photochemical smog reactions.
1. Photochemistry
Although relatively little information is available concerning
the photochemistry of ethylbenzene, styrene or its analogs, the available infor-
mation suggests that the compounds under study are not photoreactive in sunlight.
Styrene does not absorb above 300 nm, the cut-off for sunlight reaching the
earth's surface.
The irradiation of ethylbenzene in cyclohexane solution contain-
ing mercuric bromide at 254 nm gives acetophenone at approximately 17% yield
(Friedman £it a_l. , 1971). This oxidation was assigned a free radical chain
mechanism. According to Friedman and coworkers the irradiation caused forma-
tion of bromide atoms which then abstract benzylic hydrogen atoms. The benzylic
radicals then oxidize via a radical chain mechanism which probably involved a
benzyl hydroperoxide intermediate:
/T~^
HBr
CHCH
CHC1L
CHCH3 +
CHCH3 +
CHCH,
14
-------
Acetophenone was also formed when ethylbenzene was irradiated without mercuric
bromide, but the yield was only 5%.
y-Radiation of ethylbenzene produces a variety of products due
to the formation and recombination of many free radicals (Yamamoto et al.,
1971). The products include ethane, toluene, biphenyl, and diphenylpropane.
As in the above case, these reactions are probably of little significance in
the environmental chemistry of ethylbenzene.
2. Hydrolysis
Although relatively little information was available concerning
hydrolysis of ethylbenzene or the vinylbenzenes, some reasonable conclusions
can be drawn from their known chemistry and reaction mechanisms.
The vinyl benzene should hydrolyze as expected of olefins
(March, 1968). The reaction rate is expected to be acid catalyzed and neglig-
ible at pH's near neutral. The main product expected is the secondary alcohol
from styrene (or the tertiary alcohol from a-methyl styrene):
Although Boundy and Boyer (1952) mention a patent (U.S. #1,907,317) which
claims hydration of styrene to yield a mixture of a- and g-phenylethanols. no
experimental information was supplied.
Ethylbenzene is expected to be inert to aqueous hydrolysis.
When treated with very strong acids and at high temperatures, dealkylation can
proceed via a retro-Friedel-Crafts reaction (see Miscellaneous Reactions) (March,
1968).
15
-------
3. Liquid-phase Oxidation
Styrene is easily oxidized by common oxidants. This is relevant
since some of these oxidants are used for water treatment.
Aqueous chlorine (hypochlorous acid) and other aqueous halogens
add to styrene to yield chlorohydrin. The main product is expected to be B-
chloro-a-phenylethanol (March, 1968; Boundy and Boyer, 1952):
C12/H20 -—. OH
CH = CH2 > ff \- CHCH2C1
However, Boundy and Boyer (1952) have reported a British patent that claims a
mixture of the above with its isomer, a-chloro-6-phenylethanol. No experimental
details were presented. A potential hazard would result for epoxide formation
by internal S 2 reaction:
The product, styrene oxide, is a known carcinogen (IARC, 1976). Although the
reaction is known to occur in alkali, no information was available to conclude
if the epoxide forms in significant quantities at conditions present at water
treatment.
Styrene apparently ozonates by the expected route. An inter-
mediate product appears to be the oxonide:
16
-------
The oxonide can collapse to yield benzaldehyde and formic acid. In addition,
a dimeric benzaldehyde-peroxide was identified from ozonation in carbon tetra-
chloride solution (Boundy and Boyer, 1952):
Ozone also initiates polymerization of pure styrene.
Styrene is oxidized by a variety of other oxidants, including
hydrogen peroxide, permanganate, and nitric acid (Morrison and Boyd, 1974;
Boundy and Boyer, 1952). Mild oxidizing conditions produce glycols, while
strong conditions yield benzaldehyde and/or benzoic acid.
Relatively strong oxidants are required to oxidize ethylbenzene,
as with all alkyl benzenes, to yield benzoic acid (Morrison and Boyd, 1974).
Milder oxidants react with ethylbenzene to form acetophenone (Hotta and
Suzuki, 1968):
H.O./FeSO
C,H 2 2
5 dil. H2S04, 75°
Molecular oxygen reacts with the vinyl benzenes. If pure,
liquid styrene is exposed to air, the oxygen present initiates polymerization.
The oxygen reacts to form peroxides which are the polymerization chain initia-
tors of polystyrene. Higher oxygen concentrations than normally present in air
yield high molecular weight styrene peroxides. The products of slow oxidation
of styrene with oxygen give positive results with tests for carbohydrates such
as Fehling's and Tollen's (Boundy and Boyer, 1952). This suggests that products
contain polyol groupings.
17
-------
a-Methylstyrene is slowly oxidized by air to a mixture of aceto-
phenone, aldehydes, and peroxides (Boundy and Boyer, 1952). These products
increase the polymerization rate of a-methylstyrene.
Exposure of divinylbenzenes to air and direct sunlight induces
their oxidation to aldehydes and peroxides. Divinylbenzene mixtures are much
more susceptible to oxidation and polymerization than a-methylstyrene, and
hence require greater concentrations of inhibitors (about ten times higher) to
stabilize the commercial product.
4. Photochemical Smog Reaction
Although styrene and ethylbenzene are very reactive in photo-
chemical smog production, the reactions and products have not been clearly
delineated. The likely reactions and products from the styrenes and ethyl-
benzene are discussed, herein, based upon the information available from photo-
chemical smog chamber studies.
Styrenes and ethylbenzenes are among the most active generators
of photochemical smog (Levy, 1973; Laity et^ al., 1973, Darnall et al., 1976;
Altschuller and Bufalini, 1971). The relative ranking of photochemical reac-
tivity is an empirical method based upon parameters of the smog (Levy, 1973) or
indices related to the kinetics of hydrocarbon reactions with radical species
associated with photochemical smog production (Darnall £££l., 1976).
Parameters for ranking photochemical smog reactivity include rate
of hydrocarbon disappearance, oxidant production, formaldehyde production, eye
response, and time for maximum NO production. In general, the most reactive
class of organics are the olefins and the next most reactive class are the
alkyl aromatics (Laity £t a_l. , 1973; Darnall et al., 1976; Stephens, 1973).
18
-------
Olefin reactivity increases with increasing substitution of alkyl or aromatic
groups at the double bond. While a-methylstyrene is ranked as one of the most
reactive chemicals, styrene is ranked slightly less reactive but still among
the more reactive olefins. Ethylbenzene is ranked at about the same as toluene
(Levy, 1973; Laity et_ al., 1973; Darnall e£ al., 1976).
Ethylbenzene reactions under photochemical smog conditions appear
consistent with the reactions proposed for toluene. Laity et al. (1973) suggest
that the two most important reactions are the electrophilic addition of radical
species to the aromatic ring and radical reactions at the a-carbon. Radical
species, including triplet oxygen atoms and hydroxyl radicals apparently add to
the ring:
0 +
The preferred orientation would be ortho and para, addition since these would
yield maximum radical stabilization. a-Hydrogen abstraction is also expected
to participate in photochemical smog formation:
> HX
One of the expected reactions of benzyl radical is to add molecular oxygen and
yield the peroxyl radical
_CHCH3 f % \> _ CHCH, >• Products
19
-------
Laity e_t al. (1973) have identified peroxypropionyl nitrate as a product of
smog chamber reactions.
0
NO air 11
** . «Tf ^TIT t
hv
Reactivities of ethylbenzene and toluene are similar. Pitts
and coworkers (Darnall et al., 1976; Lloyd e_t al^., 1976) have measured their
reaction rates with hydroxyl radical. They reported second order rate constants
9 9
of 4.8 x 10 and 3.6 x 10 liter/mole-sec for ethylbenzene and toluene, respec-
tively, at 305°K.
Relatively little information was found which describes products
from smog chamber oxidations of the monoalkyl aromatics. The only detailed
report found was a material balance study for toluene (Spicer and Jones, 1977).
They were able to identify eight products, Table 8. Similar products are
expected from ethylbenzene irradiation. The expected products include peroxy-
acetylnitrate (PAN), peroxypropionyl nitrate, acetophenone, a-phenylethanol,
and ethylphenols.
The styrenes are more reactive in photochemical smog production
than the alkyl aromatics. The most important reaction in their decomposition
appears to be electrophilic addition (by atomic oxygen, ozone, and other species)
to the olefinic bond (Laity e£ al., 1973; Cvetanovic, 1963).
R
0 + // y-CR = CH2 >- /' y—C - CH2
0-
Pitts and coworkers (Lloyd ££ al_., 1976; Darnall e_t al., 1976) measured
reaction rates for a number of aliphatic olefins with hydroxyl radical, but no
20
-------
Table 8. Carbon Balance for Toluene - NOx System
Initial toluene
Carbon-containing compound
identified after 4 hours of
irradiation, total
Unreacted toluene
PAN (peroxyacetyl nitrate)
Benzaldehyde
Tolualdehyde
Phthaldehydes
Phenol
Cresols
Benzyl alcohol
Formaldehyde
Concentration, ppm
24.1
17.3
12.3
0.6
2.4
0.1
0.7
0.1
0.7
0.1
0.05
21
-------
information was included for the styrenes. Rate constants were 15.1 and
Q
48 x 10 liter/mole-sec for propene, and 1,3-butadiene, respectively. Since
benzene is more effective than alkyl groups in stabilizing radicals, reaction
o
rates of greater than 50 x 10 liter/mole-sec are reasonable estimates for the
rate constants.
Relatively little information was found from which to delineate
reaction products of the styrenes or a-methylstyrene in photochemical smog
chambers. If one can safely judge from products of aliphatic olefins, then
products are expected to include peroxides, formaldehyde, benzaldehyde from
styrene and acetophenone from a-methylstyrene.
5. Miscellaneous Reactions
All aromatic compounds can be reduced by catalytic hydrogenation
at high temperature and pressure. Under such conditions ethylbenzene forms
ethylcyclohexane. The vinylic benzenes undergo hydrogenation of their unsat-
urated side chains much more readily than the aromatic ring. It is, therefore,
quite easy to produce ethylbenzene by hydrogenation of styrene under appropriate
reaction conditions.
Like other alkyl benzenes, ethylbenzene undergoes electrophilic
aromatic substitution (Friedel-Crafts reaction), a technique for placing other
alkyl substituents on the ring system. A typical example is shown in Table 9.
Free radical substitution at the side chain of alkyl benzenes
occurs in the presence of light. In the absence of light, but with the aid of
a suitable catalyst, electrophilic substitution occurs on the benzene ring.
Acetophenone is produced by the catalytic oxidation of ethyl-
benzene in air, the first step in a former commercial method for the preparation
22
-------
of styrene (Hornibrook, 1962). The styrene is then formed by hydrogenation of
the acetophenone to 1-phenylethanol, followed by catalytic dehydration. Although
the styrene yields for this process are good, they are not quite as good as for
the direct dehydrogenation of ethylbenzene.
A combination of the reactions discussed thus far may form the
basis for the preparation of 2-chlorostyrene, another commercially important
copolymer of styrene:
I
HC=CH
Cl Cl Cl
Alkenes readily undergo addition of halogens, hydrogen halides,
etc. to the double bond. In vinyl benzenes, the double bonds of the alkenes
are even more reactive to such additions than aliphatic alkenes. Some examples
are given in Table 9.
The most important commercial reaction of styrene monomers is
polymerization. Styrene monomers polymerize by addition polymerization, so
called because the monomers join together without the formation of any by-products.
Addition polymerizations proceed by a mechanism involving the initial formation
of a highly reactive species such as a free radical or ion which attacks the
monomer molecule forming a new free radical or ion which in turn attacks other
monomer molecules, adding them to the growing chain. The acid catalyzed poly-
merization of styrene is illustrated in Table 9. Under environmental conditions
styrene monomer molecules would most likely be easily oxidized or hydrolyzed.
However, if enough of them are present in a confined area, such as right after
23
-------
Table 9. Miscellaneous Reactions of Styrene Monomers and
Ethylbenzene (Morrison and Boyd, 1974)
Hydrogenation
HC=CH,,
CH2CH3
CH2CH3
H2, 20°C, 2-3 atm.
Ni, 75 min.
H2, Ni, 125°C
110 atm, 100 min.
2. Electrophilic Aromatic Substitution
CH,
A1C1,
Free Radical Substitution in Side Chain
OUCH., HCBrCH,
Br,
hT
4. Electrophilic Substitution
(only product)
CH2CH3
Cl
FeCl,
5. Addition to Double Bond
Br
HCBrCH
in CC1,
6. Addition of HX
O
Cl
peroxides
HX
no peroxides
Q
HCBrCH.
-------
Table 9. Miscellaneous Reactions of Styrene Monomers and
Ethylbenzene (Morrison and Boyd, 1974) (Cont'd)
7. Polymerization
CH2=CH
H
CH CH
CH2=CH
n
CH--CH - CH. - CH - CH0 - CH
J I £• t *-
n-1
Brescia et al., 1974
25
-------
a catastrophic spill, polymerization could be a significant reaction under
certain conditions (e.g., soil could catalyze polymerization).
26
-------
II. Environmental Exposure Factors
A. Production Aspects
1. Quantity Produced, Imported and Exported
Table 10 lists the U.S. production of ethylbenzene, styrene,
a-methylstyrene, and divinylbenzene for the ten year period 1967 to 1976. The
production quantities of ethylbenzene have been estimated by assuming that
nearly all of the ethylbenzene production (minus export quantities) is used to
make styrene. Since most of the ethylbenzene producers also produce styrene,
it is not uncommon for the ethylbenzene production units to be tied on-stream
to the styrene production units to avoid storage and other costs which may be
involved. The ethylbenzene production excluding the continuous streams used
in some styrene production is also listed in Table 10. Based upon 1974 to
1976 figures, approximately 18 to 20% of the total annual ethylbenzene produc-
tion is used in continuous styrene processes.
The most recent available production figure for divinylbenzene
is 3.4 million pounds in 1972 (USITC, Annual a). However, most of the divinyl-
benzene production is consumed in the production of styrene-divinylbenzene
polymers used for ion-exchange resins. Typically, these resins contain 8%
divinylbenzene and were produced in quantities of 70 to 75 million pounds in
1974 and 1975 (Soder, 1977). Therefore, the 1974 and 1975 production volumes
for divinylbenzene can be estimated at about 5.6 million pounds annually.
Imports and exports of ethylbenzene, styrene, and a-methyl-
styrene are given in Table 11. There is no data available which indicates that
divinylbenzene is either imported or exported. As can be seen from Table 11,
imports of ethylbenzene and a-methylstyrene are virtually insignificant as
27
-------
Table 10. U.S. Production of Ethylbenzene, Styrene, a-Methylstyrene, and Divinylbenzene
00
(Quantities in Millions
* ** **
Ethylbenzene Styrene a-Methylstyrene
1976
1975
1974
1973
1972
1971
1970
1969
1968
1967
7,200
5,500
7,090
7,100
7,080
5,600
5,380
5,750
4,550
4,000
6,301
4,673
5,956
5,975
5,941
4,682
4,335
4,648
3,698
3,278
61.4
29.9
57.2
52.5
37.4
20.8
19.1
n.a.
n.a.
15.9
of Founds)
**
Divinylbenzene
n.a.
n.a.
n.a.
n.a.
3.4
2.9
3.2
3.3
2.8
2.7
**
Ethylbenzene (exclud-
ing styrene continuous
streams)
6,127
4,822
6,048
5,688
5,676
4,984
4,827
4,907
4,034
3,347
SRC Estimates
**
USITC, Annual a
-------
Table 11. Imports and Exports of Ethylbenzene, Styrene, and a-Methylstyrene
10
to
Ethylbenzene
Import si Expor t s 2
1976
1975
1974
1973
1972
1971
1970
1969
1968
1967
0.9
6.1
5.6
0
0
0
3.8
0.7
0
143
84
138
185
207
225
405
435
320
250
(Quantities in Millions of Pounds)
Styrene a-Methylstyrene
Imports^ Exports Imports1 Exports^1
24.8
6.7
60.9
30.8
21.0
0.5
9.5
13.6
9.4
16.6
952 12-24
574 0.01 n.a.
623 12
CTC
J / -f — ^^ ___
661
369
568
832
538
436
USITC, annual b
Paul and Soder, 1977
Soder, 1977; U.S. Bureau of the Census, 1976
SRC estimate
-------
compared to domestic production while imports of styrene are historically less
than 1% of domestic production. Exports are much more important; historically,
9 to 18% of the styrene produced and 1.5 to 7% of the ethylbenzene produced
domestically is exported. Exports of a-methylstyrene range from 20 to 40% of
production (Chem. Prof., 1977c).
2. Producers, Production Sites, and Major Distributors
The current producers of ethylbenzene, styrene, a-methylstyrene,
and divinylbenzene are listed in Table 12 along with their respective production
sites and available production capacities. Individual capacities are not avail-
able for divinylbenzene; however, the total current industry capacity for divinyl-
benzene can be estimated to be approximately 7 to 8 million pounds annual, based
upon current production estimates of 6 million pounds annually (SRC estimates).
Former producers of a-methylstyrene, as late as 1975, were Dow
Chemical (Midland, Mich.) and Union Carbide (Bound Brook, N.J.); they are not
producing a-methylstyrene at this time.
In general, the major distributors of these chemicals are the
producers. Other major distributors are listed in Table 13. From Table 12 it
must be noted, however, that most of the production of ethylbenzene and styrene
is captively consumed by the producers. For example, more than 90% of the
ethylbenzene production is captively consumed while approximately 50% of the
styrene production is captively consumed.
Figure 2 is a map which shows the geographical location of the
production sites for ethylbenzene, styrene, a-methylstyrene, and divinylbenzene.
The cluster of production sites in Texas and Louisiana is notable.
30
-------
Table 12. Producers of Ethylbenzene, Styrene, a-Methylstyrene, and Divlnylbenzene
Producer
Location
Ethylbenzene
Total Annual Capacity
(Millions of Pounds)
Remarks
Amoco Chem. Corp.
ARCO/Polymers Inc.
Charter Oil Co.
Cosden Oil & Chem. Co.
Cos-Mar, Inc.
Dow Chem. USA
El Pasa Natural Gas Co.
Foster Grant Co.
Gulf Oil Corp.
Joe Oil Co.
Monsanto Co.
Oxirane Chem. Co.
Phillips Petroleum Co.
Styrochem Corp.
Sun Oil Co.
Tenneco, Inc.
Union Carbide
Texas City, Tex.
Port Arthur, Tex.
Houston, Tex.
Houston, Tex.
Big Spring, Tex.
Carville, La.
Freeport, Tex.
Midland, Mich.
Odessa, Tex.
Baton Rouge, La.
Donaldsville, La.
Houston, Tex.
Alvin, Tex.
Texas City, Tex.
Channelview, Tex.
Phillips, Tex.
Penuelas, P.R.
Corpus Christi, Tex.
Chalmette, La.
Seadrift, Tex.
TOTAL
985
500
135
40
45
1520
1865
550
275
1160
615
30
1700
1160
n.a.
160
95
35
340
11,210
captive for styrene
captive for styrene
distilled from mixed xylenes
distilled from mixed xylenes; all
is sold
distilled from mixed xylenes;
captive for styrene
captive for styrene
captive for styrene
captive for styrene
partly captive for styrene
captive for styrene
captive for styrene
extracted from waste styrene tars;
all is sold
33 million Ibs/yr distilled from
mixed xylenes; captive for styrene
came on-stream in mid-1977
research grade
distilled from mixed xylenes; all is
sold
33 million Ibs/yr distilled from
mixed xylenes; captive for styrene
distilled from mixed xylenes; all is
sold
captive for styrene
-------
Table 12. Producers of Ethylbenzene, Styrene, a-Methylstyrene, and Dlvinylbenzene (Cont'd)
1*1
Producer
Location
Styrene
Total Annual Capacity
(Millions of Pounds)
Remarks
Amoco Chem. Corp.
ARCO/Polymers, Inc.
Cosden Oil & Chem. Co.
Cos-Mar, Inc.
Dow Chem. USA
El Pasa Natural Gas Co.
Foster Grant Co.
Gulf Oil Corp.
Monsanto Co.
Oxirane Chem. Co.
Texas City, Tex.
Kobuta, Pa.
Houston, Tex.
Big Spring, Tex.
Carville, La.
Freeport, Tex.
Midland, Mich.
Odessa, Tex.
Baton Rouge, La.
Donaldsonville , La.
Texas City, Tex.
Channelview, Tex.
840
440
120
90
1300
1450
400
150
990
600
1500
1000
40% captive for polystyrene mfg.
captive for polystyrene & SB latex
all may be sold
captive for polystyrene
partly captive
captive for Dow plants at eight
U.S. locations
no captive use; to be increased to
capacity of 240 million Ibs in 1978
50% captive for polystyrene
no captive use
35% captive for polystyrene, ABS, SAN
at four U.S. locations
came on-stream in mid-1977; no
Sun Oil Co.
Union Carbide
Corpus Christi, Tex.
Seadrift, Tex.
80
300
captive use
no captive use
partly captive
TOTAL 9,260
-------
Table 12. Producers of Ethylbenzene, Styrene, o-Methylstyrene, and Divinylbenzene (Cont'd)
Producer
Allied Chem. Corp.
Clark Oil & Refining
Georgia-Pacific Corp.
Getty Oil Co.
U.S. Steel Corp.
Union Carbide
ARCO/Polymers, Inc.
Dow Chem. USA
Foster Grant Co.
Location
Frankford, Pa.
Blue Island, 111.
Plaquemine, La.
El Dorado, Kans.
Haverhill, Ohio
Bound Brook, N.J.
Beaver Valley, Pa.
Midland, Mich.
Baton Rouge, La.
q-Methylstyrene
Total Annual Capacity
(Millions of Pounds) Remarks
24
5
10
2
15
_8
TOTAL 64 capacities are somewhat flexible
Divinylbenzene
n.a.
n.a.
n.a.
Sources: SRI, 1977; Soder, 1977; Paul and Soder, 1977; Chem. Prof., 1977c
-------
Table 13. Major Distributors of Styrene, Ethylbenzene,
a-Methylstyrene, and Divinylbenzene
(Chem. Mark. Reporter, 1977b; Chemical Week, 1977)
Divinylbenzene
Fallek Chemical Corp.
a-Methylstyrene
Jonas Chemical Corp.
Sattva Trading Co., Inc.
Ethylbenzene
Carbonit America, Inc.
Esselen Associates, Inc.
Montedison USA, Inc.
Stanalchem, Inc.
Stinnes Oil & Chemical Co.
Fallek Chemical Corp.
Helm Houston Chem. Corp.
Styrene Monomer
Agrimet, Inc.
Esselen Associates, Inc.
Fallek Chemical Corp.
HCI Chemicals (U.S.A.)
Helm Chemical Corp.
Holtrachem, Inc.
Hoosier Solvents & Chemicals Corp.
International Commodities Export Co.
Kah Chemical Co.
George Mann & Co., Inc.
Montedison USA
Morgan Chemicals, Inc.
Pioneer Salt & Chemical Co.
Prillaman Chemical Corp.
Southland Solvents & Chemical Co.
Stanalchem, Inc.
Stinnes Oil & Chemical Co.
T.R. America, Inc.
White Cross Laboratories, Inc.
New York, N.Y.
New York, N.Y.
Stamford, Conn.
New York, N.Y.
Stamford, Conn.
New York, N.Y.
New York, N.Y.
New York, N.Y.
New York, N.Y.
Houston, Tex.
New York, N.Y.
Stamford, Conn.
New York, N.Y.
Houston, Tex.
New York, N.Y.
Natick, Mass.
Indianapolis, Ind.
New York, N.Y.
Wellesley Hills, Mass,
Providence, R.I.
New York, N.Y.
Williamsville, N.Y.
Philadelphia, Pa.
Martinsville, Va.
Jamestown, N.C.
New York, N.Y.
New York, N.Y.
New York, N.Y.
New York, N.Y.
-------
D
I
(M
1"^
r-
in
CM
O Ethylbenzene and Styrene Production Sites
A Ethylbenzene Only Production Sites
A Divinylbenzene Production Sites
• Methylstyrene Production Sites
Figure 2. Geographical Location of Production Sites for Ethylbenzene, Styrene, Divinylbenzene, and
a-Methylstyrene
-------
3. Current Production Methods
a. Ethylbenzene
(1) Liquid-Phase Benzene Alkylation
The most widely used process in the U.S. for the pro-
duction of ethylbenzene is the liquid-phase, Friedel-Crafts alkylation of
benzene with ethylene using aluminum chloride as catalyst with ethyl chloride
or hydrogen chloride as promoters (Faith st_ al_., 1975; McDowell, 1978; Coulter
_et_ £l.., 1969). The process is schematically shown in Figure 3.
The benzene used is known as "styrene grade," which
defines a benzene with a maximum boiling range of 1°C and a minimum freezing
point of 5.3°C (dry); this ordinarily corresponds to a purity slightly above
99%. The purity of the ethylene is not a prime consideration, except that it
must be free of acetylene, other unsaturates, and moisture. In general,
ethylene of at least 90% purity is used.
The alkylation process is carried out in a brick-lined
steel tower or a glass-lined reactor operating at the boiling point of the
reaction mixture (80 to 100°C at atmospheric pressure). The conventional
reactor, which operates at about atmospheric pressure, is filled to approxi-
mately 35 feet with the liquid reactants which overflow through a line near the
top. Ethylene is introduced at the bottom of the reactor, as is the fresh
benzene, recycle benzene, recycle polyethylbenzenes, and the catalyst complex.
The catalyst complex is an oily, reddish-brown addition compound consisting of
25 to 30% aluminum chloride chemically combined with 70 to 75% of various
alkylator product compounds.
36
-------
Recycle Benzene
UJ
Ethylene
AICI3
Catalyst
Benzene
Recycle Polyelhyl Benzene
Figure 3. Ethylbenzene Manufacture Via Benzene Alkylation (Ethylene) (Adapted from Faith et al.,
1975; Coulter et al., 1969)
-------
The general chemical reaction equation which describes
a single pass of reactants through the alkylation reactor is the following
(Coulter et_ a_l. , 1969):
N^ Aid catalyst X^ \^ Unreacted Higher Mol. Wt
O + CH=CH - - - " I O I + f Q I + Benzene + Products
CH -CH
(46%) (10%) (2%)
The overall yield of benzene to ethylbenzene averages 95.5%, whereas that of
ethylene to ethylbenzene averages 96.8% (Faith et_ a_l_. , 1975).
The gaseous products, unreacted ethylene, small amounts
of benzene, hydrogen chloride, and the inerts (that were introduced with the
ethylene) leave the top of the reactor and enter a condenser from which recov-
ered benzene flows back to the alky la tor. The off-gas is scrubbed for final
benzene recovery, using recycle polyethylbenzenes as absorbent, and then is
washed with water for the removal of HC1 before venting or being compressed for
use as fuel (Coulter £t a_l . , 1969).
The liquid products from the alkylator (ethylbenzene,
unreacted benzene, diethyl- and polyethylbenzenes) are cooled and passed through
a settler where the catalyst complex is removed and returned to the alkylator.
The alkylate is then washed with water, which breaks any residual complex, and
scrubbed with 20% caustic to neutralize the acidic constituents, after which it
is separated into components in a series of distillation columns. The first
column removes the benzene for recycle to the alkylator; the second column
removes the ethylbenzene product; and the third column separates the lighter
polyethylbenzenes for recycle to the alkylator. The lighter polyethylbenzenes
38
-------
can be chemically broken down to ethylbenzene by reaction with benzene in the
reactor. The bottoms product of the third column are heavy polyethylbenzenes
and tars, which are burned as fuels.
One operating precaution is to remove the diethylben-
zene from the monoethylbenzene as completely as possible. If this is not done,
divinylbenzene will be formed in subsequent dehydrogenation steps to styrene
and, on distillation can polymerize with styrene to a cross-linked polymer
which is very hard to remove. Isopropylbenzene (cumene) should also be removed,
if formed, to prevent contamination of the styrene with a-methylstyrene and
unreacted cumene (Coulter et^ a^. , 1969).
In addition to the conventional Friedel-Crafts alkyla-
tion process (also known as the Cosden-Carbide-Badger process) described above,
two recent benzene alkylation processes have been commercially developed in the
past several years. Their main advantage over the conventional alkylation is a
substantial saving in the fuel costs. These processes are the Monsanto-Lummus
process and the Mobil-Badger process.
Monsanto-Lummus Process
The Monsanto-Lummus process is also based upon the alkylation of benzene
with ethylene; however, it does not utilize a recycling catalyst complex.
Monsanto found that the conventional catalyst phase is not only unnecessary,
but actually harmful in obtaining maximum yields (Oil and Gas J., 1976b). The
Monsanco-Lummus process uses an aluminum chloride catalyst which is contin-
uously removed and replenished with no recycle. The removed catalyst is con-
verted into an aqueous aluminum chloride solution as a by-product for water
treatment and other applications (Chemical Week, 1976). This eliminates the
problem of catalyst discharge.
39
-------
The Monsanto-Lummus process has demonstrated commercial capability at
Monsanto's 1.7 billion pounds per year ethylbenzene production facility in
Texas City, Texas which began using the process in 1974. Yields of 99% and
on-stream times of 99% were recorded in the first year of operation (Chemical
Week, 1975).
Mobil-Badger Process
The Mobil-Badger process uses a solid, non-Friedel-Crafts catalyst to
alkylate the benzene with ethylene. The catalyst, designated APEB, is a pro-
prietary development of Mobil; however, patent literature indicates that the
catalyst may be Mobil's ZSM-5, a crystalline aluminosilicate zeolite with a
unique X-ray diffraction pattern. A related compound, ZSM-12, is also a
possibility (Chemical Week, 1975).
In the Mobil-Badger process, the alkylation occurs above 700°F and at
200 to 400 psi, which are conditions differing from the conventional process.
The Mobil-Badger process makes the following environmental safety claims
(Dwyer et_ al., 1976): First, the catalyst presents no hazards or waste-disposal
problems and is environmentally inert; second, no process streams are produced
that require treatment. Besides ethylbenzene, the only streams are the light
vent gas and heavy residues, which are used as fuels.
Commercial capability of this process was demonstrated in 1975 in a 40 million
pounds per year plant operated at the Foster-Grant ethylbenzene complex in
Baton Rouge, La. (Chemical Week, 1976).
(2) Alkar Vapor-Phase Benzene Alkylation
The only vapor-phase ethylbenzene production process
commercially used is the high pressure UOP (Universal Oil Products) Alkar
40
-------
process, which uses a boron trifluoride catalyst on an inert base. This process
was designed to operate on refinery gas streams containing 8 to 10% ethylene.
Feedstocks of 5 to 100% ethylene may be used. A simplified flowsheet of the
Alkar process is shown in Figure 4.
Fresh benzene is mixed with recycle benzene and ethylene
and, after heating to reactor temperature, are fed into the fixed-bed alkylator
along with the boron trifluoride-supported catalyst. Reaction conditions are
reportedly 150 to 250°C and 400 to 700 psi (Faith ££ al., 1975). The high-
pressure effluent is then flashed and fed into the benzene recycle column where
the benzene is recovered as overhead product. The bottoms become the feed to
the second column, where the product ethylbenzene is separated from the poly-
alky Ibenzenes. Most of the polyalkyIbenzenes are recycled to a separate dealkyl-
ator along with the necessary benzene for conversion back to ethylbenzene. The
dealkylator effluent is then combined with the alkylator effluent for flashing.
The yield of ethylbenzene is reportedly quantitative with respect to benzene
after transalkylation of the polyalkylbenzenes (Coulter er^ al_., 1969). A small
purge of bottoms from the ethylbenzene column is required for removal of traces
of other alkylates formed from propylene (cumene, for example) and acetylene in
the feed of ethylene.
The Alkar process offers the advantage of less corro-
sion than the conventional aluminum chloride liquid-phase process; however, the
cost of heating fuels is substantially higher making the Alkar process unattrac-
tive with respect to conventional processes.
41
-------
Healer
Elhylene .
Fresh Benzene.—
^O^ Heater
Off Gas
Recycle Benzene
I Polyelhyl) Benzenes
Ethylbantene
a
s
g
Puro
Figure 4. Alkar Ethylbenzene Process (Adapted from Coulter et al., 1969)
-------
(3) Fractional:ion of Ethylbenzene from Mixed Xylene Streams
This process was introduced commercially by Cosden in
1957 and is schematically shown in Figure 5. Mixed xylenes occur naturally,
but only in small quantities in crude petroleum; about 0.9% by volume (Carlson,
1975). Direct separation cannot be economically justified. However, in the
initial distillation of crude petroleum into component streams, a naphtha
stream is obtained which not only contains the natural mixed xylenes, but is
rich in naphthlenes (alicyclics) and paraffins. This naphtha stream is cataly-
tically reformed to produce a high-octane gasoline rich in aromatics. Mixed
xylenes are produced, along with benzene and toluene, during the catalytic
reforming, and are taken-off in a stream known as BTX (benzene-toluene-xylene).
This BTX stream is sent to a liquid-liquid extractor to separate the benzene
and toluene from the mixed xylenes. The mixed xylene stream coming from the
extractor will vary in composition; however, a typical composition would be
ethylbenzene 20%, m-xylene 40%, o-xylene 20%, and £-xylene 20% (Carlson-, 1975).
The mixed xylene stream is sent to a fractionation
system containing three large columns in series and operated at high reflux
rates. Ethylbenzene is separated from its nearest xylene isomer, £-xylene,
which boils 3.9°F higher than ethylbenzene. The purity of the ethylbenzene
which is obtained, 99%+, is particularly important because the product styrene
purity is determined by the purity of the ethylbenzene.
The U.S. production of ethylbenzene by distillation
from mixed xylene streams is estimated to have been the following (Carlson, 1975;
SRC estimates).
43
-------
BTX Feed
r
Bciuenc and Toluene
Liquid Liquid
ExtrdClor
Mixed Xylenfl Stream
_3
5
Xylencs to Isonicr Separation
• Ethylbenzene
Figure 5. Ethylbenzene Via Mixed Xylene Fractional:ion (Adapted from Stobaugh, 1965; Coulter et al.,
1969; Carlson, 1975; Cier, 1970)
-------
Year Quantity (million Ibs) Year Quantity (million Ibs)
1976 300 1971 330
1975 270 1970 325
1974 365 1969 455
1973- 350 1968 450
1972 345 1967 395
Based upon the total ethylbenzene production estimate
of 7,200 million pounds in 1976 (Table 10), the ethylbenzene obtained from the
fractionation of mixed xylenes accounted for only 4% of the total production;
the other 96% of production came from benzene alkylation.
It is believed that due chiefly to the high energy
requirements necessary to fractionate ethylbenzene from mixed xylenes, it is
unlikely that there will be any large increases in ethylbenzene fractionation
capacity.
"The recovery of natural ethylbenzene is usually carried out as
an adjunct to the recovery of the xylene isomers but this is not
necessarily done. The ethylbenzene in the mixed xylenes can be
isomerized to maximize ortho- and para-xylene recovery. It is
probable that the isomerization technique will be used to an
increasing extent. Thus, the isolation of ethylbenzene from
mixed xylene streams may continue to decline at the same time
that the isolation of the individual xylene isomers continues
to increase" (Carlson, 1975).
(4) Extraction from Styrene Tars
Joe Oil Aromatics (a division of Joe Oil, Inc.) in
Houston, Texas, treats waste tars from chemical plants. One treatment involves
extraction of ethylbenzene from styrene tars. Capacity for ethylbenzene extrac-
tion is 30 million pounds per year (Paul and Soder, 1977).
b. Styrene
At present, most of the styrene produced in the U.S. is made
by the dehydrogenation of ethylbenzene in vapor phase. However, in late 1977
45
-------
Oxirane (Channelview, Texas) brought on-stream a plant which produces styrene
as a co-product from propylene oxide manufacture.
(1) Dehydrogenation of Ethylbenzene
Ethylbenzene is dehydrogenated to styrene by the
following reaction, which is endothermic:
The above reaction is the desired selective reaction; however, various non-
selective reactions will also occur. For example, benzene and toluene are
produced in quantities which average 0.7% and 1.0% of reactor effluent, respec-
tively (Faith et^ al_., 1975). The purity of the ethylbenzene feed, which must
be 99% or better, is of prime importance. Contaminants, such as diethylbenzene,
will also be dehydrogenated and will produce products which form unwanted poly-
mers.
A schematic of the general industry production method
is given in Figure 6. Purified ethylbenzene is preheated, first with steam (to
160°C), and then by heat exchange (to 520°C) with the effluent reactor products.
Superheated steam (710°C) and ethylbenzene vapors are continuously mixed and fed
into a reactor at a ratio of 2.6 kg steam/kg ethylbenzene. The reactor contains
a selective fixed-bed dehydrogenation catalyst such as zinc, chromium, iron, or
magnesium oxide, on activated charcoal, aluminas, or bauxites. The catalyst
operates continuously and has a production life of 1 to 2 years. At a catalyst
temperature of about 630°C, resulting from the vapor-feed temperature, conversions
of 35 to 40% per pass of reactants through the reactor may be realized. Usual
overall yields of 90% ethylbenzene to styrene are realized.
46
-------
Recycle Ethylbenzene
Ethylbenzene
Steam
Benicne and Toluene
Tar
Wastewater
Styrcne
Inhibitor
Tar Residues
Figure 6. Styrene Production Via Ethylbenzene Dehydrogenation (Adapted from Faith ej^
Austin, 1974; Coulter et al. , 1969)
^. , 1975;
-------
The reaction products leave the top of the reactor at
about 565°C and are cooled by the influent ethylbenzene in heat exchangers.
A spray-type cooler lowers the product temperature to about 105°C and condenses
out some of the tars which may contain some stilbene and biphenyl. A final
condenser liquifies the steam (styrene, toluene, and benzene) while the vent
gases containing hydrogen, carbon monoxide, carbon dioxide, and lower aliphatic
hydrocarbons are sent to a refrigerated recovery system. The condensed mater-
ials pass to a settling tank, where the hydrocarbons are decanted and the water
is discharged to a disposal system.
The crude styrene, of average composition 37% styrene,
61% ethylbenzene, 1.0% toluene, 0.7% benzene, and 0.3% tars, is passed through
a pot containing sulfur or some other polymerization inhibitor and is then fed
to a vacuum column system. The overhead from a primary fractionating column is
fractionated to separate the ethylbenzene, which is recycled, from the benzene
and toluene, which are separated by distillation. The bottoms from a primary
fractionating column are distilled to obtain the styrene product. A polymeriza-
tion inhibitor, usually TBC (tert-butylcatechol), is added at the top of the
column to prevent the styrene from polymerizing. The tar residue discharged
from the finishing column bottom is sometimes buried, but Dow Chemical (Burgess,
1978) recommends using it for fuel. Union Carbide has just submitted an 8e
notice to EPA under TSCA indicating that these polyethylated benzene tails
"appear to be unequivocally highly carcinogenic in mice" (Toxic Materials News,
1978). The distilled styrene passes to receivers, where more inhibitor (TBC)
is added to bring its concentration to 10 ppm. The finished material is
refrigerated below 20°C and loaded to insulated tank cars for shipment (Faith
etal., 1975; Austin, 1974; Coulter et_ al., 1969).
48
-------
(2) Co-Product with Propylene Oxide
In late 1977, Oxirane Corp. brought into production a
plant which makes styrene by the following method (Soder, 1977):
C,H,CH,CH, + 0
O J £ J
(ethylbenzene)
>• C,H,CHOOHCH,
0 5 3
(ethylbenzene hydroperoxide)
0
/\
C H CHOOHCH3
(propylene)
(methyl phenyl (propylene oxide)
carbinol)
(styrene)
Ethylbenzene is oxidized to its hydroperoxide which is
then reacted with propylene to yield propylene oxide and co-product methyl
phenyl carbinol. The carbinol is then dehydrated to styrene.
c. a-Methylstyrene
(1) By-Product from Cumene-Phenol Process
The purification of small amounts of a-methylstyrene
formed as a by-product in the cumene-phenol process is the most important
industrial source of the monomer. At present, this is the only commercial
source of a-methylstyrene as Dow's process of dehydrogenating cumene to a-
methylstyrene has been shut-down.
In the industrial process which converts cumene into
phenol and acetone, a-methylstyrene represents about 1.7% of the total cumene
conversion (Coulter et_ al., 1969). In order to recycle cumene in this oxidative
49
-------
process, it must be essentially free of a-methylstyrene. Therefore, the hydro-
carbon streams from the reaction must be subjected to a series of fractional
distillations to remove this unwanted material. At present, some phenol manu-
facturers employing the cumene process find it more economical to hydrogenate
the a-methylstyrene back to cumene and convert it to more phenol and acetone.
Others have chosen to install additional finishing facilities for the monomer
and market the product.
(2) Dehydrogenation of Cumene
Through 1975, Dow Chemical produced a-methylstyrene by
direct dehydrogenation of cumene. In a typical operation, a mixture of three
parts steam to one part cumene is passed rapidly over an iron oxide dehydrogen-
ation catalyst at elevated temperatures. The crude dehydrogenation mixture
consists of cumene and a-methylstyrene, as well as small amounts of benzene,
toluene, ethylbenzene, and styrene. The economical operation of this process
demands that all of these components be separated and purified for reuse; this
is accomplished through a series of fractional distillations (Coulter et_ al.,
1969).
d. Divinylbenzene
Divinylbenzene is manufactured by the dehydrogenation of
mixed isomeric diethylbenzenes. The diethylbenzenes used in the manufacture of
divinylbenzene are side products produced in the manufacture of ethylbenzene by
the alkylation of benzene with ethylene. Normally, these higher alkylated pro-
ducts are separated and recycled for dealkylation in the ethylbenzene production
process. However, it is a simple matter to retain some of the diethylbenzene
stream for making divinylbenzene. This diethylbenzene stream, from a typical
50
-------
alkylation, will consist of a mixture of the three possible isomers of diethyl-
benzene in the proportions 9.4%:61.5%:29.1% (£, m, £, respectively) and some
sec-butyl- and isobutylbenzenes, which are separated from the diethylbenzenes
before cracking (Coulter et_ al., 1969).
Dehydrogenation of diethylbenzenes is accomplished in the
following way:
"Dehydrogenation of the three isomers is carried out in an
apparatus very similar to that used for styrene. Preheated
vapors of the hydrocarbons are mixed with superheated steam
and passed over catalysts of mixed metal oxides at tempera-
tures around 600°C. The presence of two ethyl groups on the
aromatic ring greatly increases the number of possible pro-
ducts. The major portion of the reaction effluent consists
of m- and £-divinylbenzene, the corresponding ethylvinyl
compounds, and some unreacted diethylbenzene. Essentially
all of the o-diethylbenzene is isomerized to naphthalene in
the dehydrogenation process. Minor contaminants also found
are benzene, toluene, vinyltoluenes, ethyltoluenes, xylenes,
ethylbenzene, and styrene. The distillation and finishing
of this mixture is an extremely sensitive procedure since
divinylbenzene polymerizes very readily even at moderate
temperatures. The finishing may be carried out in a series
of three columns [as shown in Figure 7]. In the first column
a rough separation of the monomers from the lighter materials
is accomplished. Benzene, toluene, xylene, ethylbenzene,
styrene, diethylbenzene, vinyltoluenes, ethyltoluenes, and
some ethylvinylbenzenes are collected as distillates and
subjected to further fractionation in column 2, where the
lower-boiling materials are taken overhead to be sold as
solvent or burned. It is impractical to recover styrene
from this stream due to the likelihood of contamination with
divinyl materials. The bottoms product of column 2, which is
primarily diethylbenzene with some ethylvinylbenzene, is re-
turned to the dehydrogenation reactor. Bottoms product from
column 1, which contains most of the ethylvinylbenzene and the
divinyl compounds plus some higher-boiling materials, is taken
to column 3. Here, under a vacuum of 10-15 mm, a final distilla-
tion to remove the naphthalene and tars is carried out. Appro-
priate inhibitors are employed throughout this step to limit
the polymerization of the monomers. For commercial production
no attempt is made to further purify the monomer and it is gen-
erally sold as a mixture of components, chiefly divinylbenzene
and ethylvinylbenzene. For most applications divinylbenzene is
used in low concentrations as a crosslinking agent and additional
purification is neither necessary nor desirable (Coulter ££ a_l., 1969)."
51
-------
3
I
Crude
Dehydrogenation
Mixture
Benzene
Toluene
Xylene
Ethylbenzene
Styrene
Diethylbenzene
Vinyltoluene
Ethyltoluene
(Ethylvinylbenzene)
_^J Ethylvinylbenzene
~~ I diethylbenzene
i Solvent or Fuel
To Dehydrogenator
— I Finished Divmylbenzene-
Ethylvmylbenzene Mixture
Naphthalene Tar
Figure 7. Finishing Distillations Used in the Manufacture of Commercial
Divinylbenzene Monomer (Coulter ££ al., 1969)
52
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4. Market Price and Trends
The market prices of ethylbenzene, styrene, a-methylstyrene, and
divinylbenzene are listed in Table 14 for the period 1968 through the present.
a. Ethylbenzene
In addition to demand requirements, the market price of
ethylbenzene is dependent upon the raw material costs of ethylene and benzene.
In 1975, ethylbenzene production made up about 44% of the total benzene demand
and 6% of the ethylene demand; these figures will rise to 50% of the benzene
demand and 5% of the ethylene demand in 1985 (Chem. & Eng. News, 1977). Raw
material benzene prices have been projected to rise from the 1975 level of
$0.80 per gallon to $1.07 per gallon in 1980 and to $1.18 per gallon in 1985
(Chem. & Eng. News, 1977); however, more recent projections (Chem. & Eng. News,
1978) indicate that benzene prices may stabilize near $0.85 to 0.90 per gallon.
Therefore, ethylbenzene prices will probably not rise significantly in the near
future. Long term projections are not certain at this time.
Figure 8 diagrams ethylbenzene production by year and gives
a graphical illustration of past market trends as well as future trends which
have been forecasted. The historical growth of the ethylbenzene market has
averaged about 9.3% per year (Chem. Prof., 1975). The decline in 1975 is
attributed to the general economic recession during that year (Paul and Soder,
1977). Future growth is expected to average about 5% per year (Chem. Prof., 1975),
At the present time, 97% of the ethylbenzene production is
used to manufacture styrene. Production increases or decreases of the two
chemicals are directly related. Increased, growth for ethylbenzene is dependent
upon growth in the production of styrene-containing plastics.
53
-------
*
Table 14. Market Prices of Ethylbenzene, Styrene, a-Methylstyrene, and Divinylbenzene
1977
1976
1975
1974
1973
1972
1971
1970
1969
1968
Ethylbenzene
.14
.14
.09
.173
.05
.03
.04
.04
.03
.04
Styrene
.21
.20
.19
.172
.07
.06
.06
.06
.06
.07
(Dollars per pound)
a-Methylstyrene
.15
—
.12
.115
.06
.05
.06
.06
.10
.08
Divinylbenzene
50-60%
.63
.63
—
—
—
.64
.65
.67
.70
.72
20-25%
.25
.25
—
—
—
—
—
—
—
—
Source: US1TC, Annual a; Chemical Marketing Reporter; Paul and Soder, 1977; Industrial Contacts
-------
_ - 6000
•5000
— 4000
1960 1965 1970 1975
Years
1980
S
3000
o
M
e
o
— 2000
_ - 1000
1985
Figure 8. Ethylbenzene Production by Year
55
-------
b. Styrene
According to Charles V. Sleeth, Vice President of Marketing
at Foster Grant Co. (Chem. & Eng. News, 1977), about 30% of the 1976 styrene
capacity is in smaller, older, and less efficient plants. At current prices,
Sleeth suspects that these plants' raw material and fuel costs are about 1.5
cents per pound of styrene higher than the larger modern plants. As industry
is required to use higher priced fuels or other fuel sources, this cost dis-
advantage could increase to 4 cents per pound. Therefore, a number of older
units may be expected to shut down in the next four or five years. Sleeth
says that even for the newer and more efficient plants, fuel costs per pound
could jump 2 cents to 2.5 cents.
Sleeth is predicting a growth rate of 6% per year to 1980
and 5% per year through 1985. The major factor affecting the long-range market
is the rise in oil prices. Over the next few years, higher energy costs will
lead to shifting patterns of demand. Sleeth thinks that these shifts will
increase the demand for plastics, the major market for styrene; the trend for
substituting plastics for other materials may even accelerate.
Chem. Prof. (1977d) is predicting a growth rate of 5% per
year through 1981 for styrene. Currently, styrene is selling for $0.195 per
pound which is down from the earlier 1977 prices of $0.21 per pound. This is
primarily due to discounting of benzene used for raw material. As mentioned
earlier, benzene prices may have temporarily stabilized near $0.80 per gallon.
An increase in benzene prices, however, will cause styrene prices to rise.
c. a-Methylstyrene
Historically (1967 to 1976), a-methylstyrene production has
56
-------
grown at a rate of 11% per year; future projections indicate that production
will grow at an average rate of 6% per year through 1981 (Chem. Prof., 1977c).
There is a large demand for ct-methylstyrene both domestically and abroad,
primarily for its use as an acrylonitrile-butadiene-styrene (ABS) additive
for automotive products. These a-methylstyrene resins are useful in producing
lighter, and thereby, more fuel efficient cars.
Growth will be supply-limited because a-methylstyrene is
produced as a by-product of cumene-phenol operations which are experiencing low
'operating rates (Chem. Prof., 1977c). Exports of high-purity a-methylstyrene
have been healthy thus contributing to a tight market domestically. These
factors may be reflected in an upward trend in prices.
d. Divinylbenzene
As compared to the other chemicals being studied in this
report, divinylbenzene has been produced in only small quantities, 2.7 to 5.6
million pounds per year. However, the current outlook for the divinylbenzene
market is quite good. Divinylbenzene is primarily used to make styrene-divinyl-
benzene resins which have applications in ion-exchange resins.
Average growth on the order of at least 8 to 10% per year
for styrene-divinylbenzene resins is anticipated by most industry sources for
1976 to 1980 period, with some predicting average annual growth as high as 15%.
Growth is expected to result primarily from increasing ion-exchange resin
requirements of both municipal and industrial wastewater treatment facilities
(Soder, 1977). By 1980, production of divinylbenzene may reach 9 to 11 million
pounds, while by 1985, production may total 15 to 20 million pounds.
5. Quantity Produced as Contaminant of Other Materials
a. Ethylbenzene and Styrene
57
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Listed below is a summary of the quantities of ethylbenzene
and styrene which exist as a contaminant or ingredient of materials:
Quantities in Millions of Ibs./Year
Source Ethylbenzene Styrene
Catalytic reformate 9,400-10,000
Pyrolysis gasoline 57-96 228-342
Polymers & resins 2-3 4-5
As explained in Section II. A. 3. a. (3), ethylbenzene is
commercially produced by distilling the mixed xylene stream obtained by cataly-
tically reforming the naphtha stream of crude petroleum. Only a small percentage
of the total catalytic refonnate output is used to isolate a mixed xylene
product; most of it is blended into gasoline. In 1974, approximately 47,000
to 50,000 million pounds of mixed xylene were produced in catalytic reformate,
but only 5,791 million pounds were isolated as a product (Carlson, 1975).
Approximately 20% of mixed xylene is ethylbenzene.
The large amounts of catalytically reformed mixed xylenes
blended into gasoline is reflected in the detectable quantity of ethylbenzene
found in gasoline. Approximately 1.92% (by volume) of regular grade gasoline
is ethylbenzene and 3.12% (by volume) of premium grade gasoline is ethylbenzene
(Stavinoha and Newman, 1972). Ethylbenzene also exists naturally in crude
petroleum at a concentration of 0.094% by weight (Martin and Winters, 1963).
Pyrolysis gasoline is obtained when paraffins, condensates,
naphtha, and gas oil are cracked with intention of producing ethylene. Approx-
imately 50 to 70 million pounds of pyrolysis gasoline are obtained for every
100 million pounds of ethylene produced (Carlson, 1975). The mixed xylenes
comprise 10 to 12% by weight of this pyrolysis gasoline (Carlson, 1975) while
58
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4 to 6 million pounds of styrene are produced per 100 million pounds of ethylene
(Soder, 1977). Toray Industries of Japan is commercially developing a process
to obtain the styrene portion of pyrolysis gasoline (Soder, 1977).
When styrene monomer is used to produce polymers and resins,
a small percentage of styrene monomer will remain as a contaminant in the
polymerized product. Approximately 0.10% styrene monomer and 0.06% ethylben-
zene are present in a final polystyrene product (see Section II. B. 1. b. (1)).
In 1976, about 4,200 million pounds of styrene copolymers were produced (Soder,
1977).
b. a-Methylstyrene and Divinylbenzene
If we assume that about 0.10% a-methylstyrene and divinyl-
benzene monomer remain as contaminants in their polymer products, then less
than 100,000 pounds per year of each of the chemicals, contaminates their
respective products.
B. Use Aspects
1. Consumption and Use Data
a. Ethylbenzene
Ethylbenzene consumption can be broken down as follows
(SRC estimates; Paul and Soder, 1977):
Production of Styrene 97.5-98.5%
Exports 1.5-2.5%
Solvents . <1%
100%
Styrene production is described in detail in Section II. A.
3. b., and will not be discussed here. Approximately 2.5% of the domestic
ethylbenzene production was exported in 1976 (U.S. Bureau of the Census, 1976);
59
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however, ethylbenzene exports may decline slightly in future years as production
facilities come on-stream in foreign countries (Paul and Soder, 1977). Solvent
use of ethylbenzene has been declining in recent years; it is used as a general
purpose solvent, usually in combination with other solvents, in industrial
plants.
b. Styrene
Table 15 lists the styrene consumption by end-use in 1975
and the estimates which are projected for 1980. The general recession in 1975
caused styrene consumption to decline almost 24% from the 1974 level; however,
the percentage breakdown given in Table 15 is still quite accurate. Table 16
gives the estimated consumption of styrene by consumer and industrial product
end-use markets in 1974; here, the emphasis is given to the final end-use pro-
duct. A general description of the various uses listed in Table 15 follows.
(1) Polystyrene
About 55% of all styrene consumed in the U.S. is used
to make polystyrenes. The polymerization of styrene is a chain reaction which
proceeds readily by all known polymerization techniques; the reaction can be
shown schematically as (Griffin and Glass, 1974):
5
The polymer can be characterized by the distribution of n values. The polymer-
ization reaction is activated by heat alone; however, peroxides are used commer-
cially to accelerate the process (Haddad, 1976).
60
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Table 15. Styrene Consumption by End-Use in 1975 and Estimates for 1980
(adapted from Soder, 1977; Chem. & Eng. News, 1977)
1975
Styrene Consumption
(Millions of Founds) Percent
Straight Polystyrene
Impact Polystyrene
ABS Resins
SAN Resins
Styrene-Butadiene Copolymer Latexes
Other Copolymers over 50% Styrene
SBR Elastomers
Unsaturated Polyester Resins
Misc. Polymers less than 50% Styrene
Exports
Other
1,383
1,278
347
61
287
81
459
312
50
574
<5
28.5
26.5
7
1.5
6
1.5
9.5
6.5
1
12
<1
1980
Styrene Consumption
(Millions of Pounds) Percent
4,100
750
125
410
142
625
520
100
685
<5
55
10
1.5
5.5
2
8.5
7
1.5
9
< 1
TOTAL
4,837
100%
7,462
100%
-------
Table 16. Estimated Consumption of Styrene by Consumer and
Industrial Product End-Use Markets - 1974 (Soder, 1977)
Estimated Consumption
(Millions of Pounds) Percent of Total
Packaging 1,100 22
Construction-Related Markets 789-797 16
Construction 261-265
Pipe 253-255
Industrial rubber products 177
Lighting fixtures and signs 50
Paint 22
Corrosion-resistant products 26-28
Electrical, Appliance, TV, Communica-
tion, and Office Machines-Related Markets 620-624 12
Appliance and 'TV 339
Electrical and other 281-285
Household (except appliances) 582-589 12
Housewares and furnishings 285
Carpeting and flooring 151
Furniture 116-120
Synthetic marble 30-33
Transportation-Related Markets 477-484 10
Tires 315
Auto, truck, bus parts 139-142
Auto putty 15-19
Miscellaneous transportation 8
Recreation-Related Markets 408-414 8
Toys, sporting goods, miscellaneous
recreational articles 322-324
Marine (pleasure boats) 52-56
Recreational vehicles 34
Disposable Serviceware 230 4
62
-------
Table 16. Estimated Consumption of Styrene by Consumer and
Industrial Product End-Use Markets - 1974
(Soder, 1977) (Cont'd)
Miscellaneous 536-546 11
Industrial products 233-238
Paper coatings & additives 128
Ion-exchange resins 45-50
Medical/dental/lab equipment 50
Impact modifiers 10
Consumer products 214-216
Novelties & other uses 95
Writing utensils 54
Personal care items 50
Luggage & cases 11
Floor polishes 4-6
Other 89-92
Exports 241-243 5
TOTAL 4,933-5,027 100%
63
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Two general classes of polystyrenes are produced: (1)
"straight" or homopolymer polystyrenes and (2) impact or "rubber modified"
polystyrenes. Straight polystyrene is a water-white, transparent plastic with
an unlimited colorability range which is widely used in packaging, toys, house-
wares, and appliances. It can easily be molded or extruded into practically
any shape or form. Expanded foams of polystyrene have excellent heat-insulat-
ing and flotation properties and find application in construction and refriger-
ation, as well as numerous uses in packaging and drinking cups. Impact poly-
styrenes contain 3 to 10% elastomer (e.g., polybutadiene), which decreases the
brittleness of the resin and considerably expands the number of applications.
It is not transparent like the homopolymer, but it is much more durable.
Packaging applications account for about one-third the use of all polystyrenes
produced (Soder, 1977).
As might be expected, a small amount of styrene monomer
remains in the final polystyrene product as a contaminant. Table 17 below gives
an analysis of styrene monomer and ethylbenzene content in various polystyrene
products chosen at random.
Table 17. Analysis of Various Grades of Polystyrene
(Crompton and Myers, 1968).
Weight per cent
Component
Styrene
Ethylbenzene
Crystal
grade
0.033
0.066
Expandable
grade
0.32
0.081
Self
extinguishing
grade
0.080
0.047
High
impact
grade
0.18
0.086
Foodstuff
packaging
grade
0.04
0.06
64
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Approximately 3,200 million pounds of polystyrenes
were produced in 1976 (Soder, 1977). If we assume that 0.10%, on average,
styrene monomer remains in the polystyrene as contaminant, then 3.2 million
pounds of styrene contaminated polystyrene products in 1976. Similarly,
assuming ethylbenzene at 0.06%, on average, yields 1.92 million pounds of
contamination.
(2) ABS Resins
ABS (acrylonitrile-butadiene-styrene) resins are
produced by the co-polymerization of acrylonitrile and styrene monomers in the
presence of butadiene rubber. The resultant styrene-acrylonitrile (SAN) co-poly-
mers are grafted onto the rubber particles to yield hard, tough, chemically
resistant plastics (Morneau, 1976). ABS resins typically contain 50 to 60%
styrene (Soder, 1977); however, after polymerization, the final product will
contain only a small percentage of styrene monomer.
Uses for ABS resins are the following (Chem. Prof.,
1977a): pipes and fittings (drain, waste, and vent), 29%; automotive, 18%;
large appliances, 14%; small appliances, 5%; recreational vehicles, 8%; business
machines and telephones, 5.2%; furniture, luggage, and packaging, 6.1%; exports,
3.2%; miscellaneous, 11.5%.
(3) SAN Resins
SAN (styrene-acrylonitrile) resins are transparent,
rigid thermoplastics with properties slightly different and somewhat intermediate
to those of polystyrene and ABS. They are produced by the copolymerization of
styrene, 60 to 80%, and acrylonitrile, 20 to 40% (Soder, 1977). Application of
SAN resins include automobile instrument panel windows and lenses, clear houseware
items, and appliances.
65
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(4) Styrene-Butadiene Copolymer Latexes
Styrene-butadiene copolymer, which contains upward of
50% styrene (as compared to synthetic styrene-butadlene rubber which is made
from the same ingredients but is only 20% styrene), is a latex material used as
an emulsion in the manufacture of paint and surface coatings for cloth and
paper. The primary uses are carpetback coatings and paper coatings.
(5) Other Copolymers Over 50% Styrene
Styrene-divinylbenzene resins, the most important
copolytner of this classification, are formed by crosslinking polystyrene beads
with divinylbenzene and are the most common matrix base for ion exchange resins.
Typically, styrene-divinylbenzene ion-exchange resin is produced from 92%
styrene and 8% divinylbenzene. The major uses of ion-exchange resins are
water-treatment (softening and deionization) and chemical processing. In 1975,
64 to 69 million pounds of styrene were consumed in production of styrene-
divinylbenzene resins (Soder, 1977).
Less than 5 million pounds of styrene were consumed in
1975 in the production of styrene-maleic anhydride copolymers. They are used
in floor polishes, textile and paper sizing, rug shampoos, and latex paint. The
styrene/maleic anhydride mole ratio is typically 1:1 to 3:1 (Soder, 1977).
®
K-Resiir* is a transparent styrene-butadiene copolytner
film, sheet, and injection molding resin that is believed to contain 75% styrene
and 25% butadiene. It has been made since 1973 by Phillips Petroleum; plant
capacity is currently 18 million pounds per year (Soder, 1977).
Methyl methacrylate-butadiene-styrene (MBS) resins are
used as impact modifiers for rigid PVC; commercial development was only begun in
66
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1974. Industry capacity for MBS resins is at least 35 million pounds per year
(Soder, 1977).
(6) SBR Elastomers
Styrene-butadiene elastomers (SBR) account for the
bulk of all elastomers used in passenger cars and lightweight truck tires. The
newer SBR polymers contain about 21% styrene (Soder, 1977). When more than 50%
styrene is used in combination with butadiene, the resulting polymers generally
are more like plastics than rubbers. SBR elastomers find the following appli-
cations (Chem. Prof., 1977b): tires and tire products, 68%; molded and extruded
goods, 13%; sponge, 4%; footwear, 3%; miscellaneous, 12%.
Vinyl pyridine-styrene-butadiene latexes, which are
included in SBR production data, are primarily used in tire cord adhesives.
(7) Unsaturated Polyester Resins
Unsaturated polyester resins are thermosetting resins
used primarily in fiberglass reinforced plastics (FPP) for marine, construction,
and transportation applications; other products include synthetic marble and a
variety of consumer goods (Soder, 1977).
The resins are formed by polycondensation of dicarb-
oxylic acids or anhydrides (such as maleic anhydride, phthalic anhydride, and
isophthalic acid) with glycols (such as propylene glycol and ethylene glycol);
the polycondensate is then dissolved in styrene, which, when catalytically
activated, crosslinks through the unsaturated bonds of the dicarboxylic acids
or anhydrides. Actual compositions of polyester resins vary widely, but typical
styrene content is in the range of 30 to 50 weight percent of the final resin
product (exclusive of reinforcement) (Soder, 1977).
67
-------
(8) Miscellaneous Polymers Less Than 50% Styrene
Acrylic ester-styrene copolymers used in acrylic thermo-
setting solvent-based surface coatings typically contain 0 to 50 weight percent
styrene in combination with ethyl acrylate and acrylamide. These coatings are
used in industrial applications, primarily in topcoats for automobiles, trucks,
and buses. Styrene consumption for these copolymers is estimated at 19 to 22
million pounds annually (Soder, 1977).
Acrylic and methacrylic ester-styrene copolymers con-
taining 1 to 20% styrene are used in floor polish formulations. Maximum styrene
consumption for these products is estimated at 4 to 6 million pounds per year
(Soder, 1977).
Styrene-polydiene block copolymer thermoplastic elas-
tomers, that contain 70% butadiene (or isoprene) and 30% styrene, are used in
footwear, adhesives, and miscellaneous molded and extruded goods. Styrene
consumption for this use may have been 9 to 11 million pounds in 1975.
Styrenated alkyds for use in alkyd surface coatings
are generally formed by adding styrene modifier to a preformed alkyd resin; up
to 40% styrene can be added, but 10 to 25% is more common. Styrene consumption
for this production is probably a maximum of 7 to 8 million pounds annually.
(9) Other
Styrenated phenols are used as rubber antioxidants;
total production of Styrenated phenols was 2.1 million pounds in 1974 and 0.5
million pounds in 1975 (USITC, Annual a). About 1 to 2 million pounds per year
of styrene oxide are produced; styrene oxide can be used as a reactive diluent
in epoxy resin manufacture and in specialty polyol manufacture (Soder, 1977).
68
-------
Styrene oxide is produced by Union Carbide at Taft, Louisiana (SRI, 1977).
Small amounts of styrene are also used in the production of styrenated oils
(Soder, 1977).
c. a-Methylstyrene
Virtually all of the a-methylstyrene that is commercially
recovered is used in the formulation of specialty polymers and resins. It is
widely used in modified polyester and alkyd resin formulations where its dis-
tinctive properties, such as light color, are valuable. Copolymers of a-methyl-
styrene and methylmethacrylate have high heat-distortion resistance properties
and have been approved for use in food applications. Low-molecular-weight
a-methylstyrene polymers are viscous liquids that are used as plasticizers in
paints, waxes, adhesives, and plastics. The main use in specialty resins appears
to be in ABS resins used in automobiles (Chem. Prof., 1974a; Coulter et al.,
1969).
More than 20% of the domestic production has been exported
in recent years; expansion of domestic production was apparently done to serve
the increased demand in the export market (Chem. Prof., 1974a).
d. Divinylbenzene
Most of the divinylbenzene production is used in the manu-
facture of ion-exchange resins. Styrene-divinylbenzene resins formed by cross-
linking polystyrene beads with divinylbenzene are the most common matrix base
for ion-exchange resins. A typical styrene-divinylbenzene resin contains 92%
styrene and 8% divinylbenzene. Other ion-exchange matrixes made from divinyl-
benzene include methyl acrylate-divinylbenzene copolymers (Soder, 1977). The
major uses of these ion-exchange resins are water-treatment (softening and
deionization) and chemical processing (such as, sugar purification, pharmaceutical
69
-------
manufacture, and uranium processing). Divinylbenzene also finds applications
in styrene-butadiene rubber; the swelling, shrinkage, and extrusion properties
of the product are improved by adding small amounts of the monomer to the formu-
lation (Coulter et^ al_., 1969).
2. Use Sites
Table 18 lists the use sites for styrene and divinylbenzene
monomers. Ethylbenzene use sites are basically the styrene production sites.
a-Methylstyrene is mainly used in ABS-type resins, so the ABS production sites
listed in Table 18 may be a good indication of the use sites for a-methylstyrene.
Amoco Chemicals (Texas City, Texas) produces a linear a-methylstyrene polymer
(SRI, 1977).
3. Application of Products Containing Contaminants
Most of the polymer products made from the subject chemicals
will contain a small percentage of the monomer as a contaminant in the final
product. The application of these polymer products has previously been described
in Section II. B. 1. Corporate tradenames for various polymer products are
given in Table 19.
a. Ethylbenzene
The major product which contains ethylbenzene as a contam-
inant is mixed xylenes (see Section II. A. 5). Most of these xylenes are never
isolated from the refinery streams of which they are components, but are simply
blended into gasoline because of the high octane rating of mixed xylenes. The
mixed xylene which is isolated has several applications. Most importantly, it
is used as a source of the individual isomers of xylene and as a source for
commercial ethylbenzene (see Section II. B. 3. a. (3)). In 1974, 150 million
70
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Table 18. Use Sices for Styrene and Divinylbenzene Monomer
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
A & E Plastik Pak Co. City of Industry, Calif.
Abtec Louisville, Ky.
Alpha Chem. Corp. Colliersville, Tenn.
Kathleen, Fla.
Riverside, Calif.
American Cyanamid Azuza, Calif.
Wallingford, Conn.
American Synthetic Rubber Louisville, Ky.
Amoco Chem. Co. Joliet, 111.
Medina, Ohio
Torrance, Calif.
Williow Springs, 111.
ARCO Chem. Channelview, Tex.
ARCO/Polymers Inc. Beaver Valley, Pa.
Ashland Oil Co. Bay town, Tex.
Calumet City, 111.
Los Angeles, Calif.
Newark, N.J.
Pensacola, Fla.
Valley Park, Mo.
BASF Wyandotte Jamesburg, N.J.
Beatric Food Co. Wilmington, Mass.
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Table 18. Use Sites for Styrene and Divinylbenzene Monomer (Cont'd)
(SRI, 3977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
Borden Inc. Bainbridge, N.Y.
Compton, Calif.
Demopolis, Ala.
Illiopolis, 111.
Leorainster, Mass.
Borg-Warner Ottawa, 111.
Washington, W.Va.
Cargill, Inc. Carpentersville, 111.
Lynwood, Calif.
Celanese Corp. Charlotte, N.C.
Cook Paint & Varnish Co. Detroit, Mich.
Milpitas, Calif.
North Kansas City, Mo.
Co polymer Rubber & Chem. Baton Rouge, La.
Cosden Oil & Chem. Big Spring, Tex.
Calumet City, 111.
Deering-Milliken Inman, S.C.
Dewey and Almy Chem. Owensburg, Ky.
South Acton, Mass.
Diamond Shamrock Deer Park, Tenn.
Oxnard, Calif.
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Table 18. Use Sites for Styrene and Divinylbenzene Monomer (Cont'd)
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
Dow Chem. Allyn's Point, Conn.*
Dalton, Ga.
Freeport, Tex.
Gales Ferry, Conn.*
Ironton, Oh.
Magnolia, Ark.
Midland, Mich.
Pevely, Mo.
Pittsburg, Calif.
Torrance, Calif.
Firestone Tire & Rubber Akron, Oh.
Pottstown, Pa.
Lake Charles, La.
Foster Grant Chesapeak, Va.
Leominster, Mass.
Peru, 111.
Freeman Chem. Corp. Chatham, Va.
Saukville, Wise.
GAP Corp. Chattanooga, Tenn.
General Tire & Rubber Mogadore, Oh.
Odessa, Tex.
B.F. Goodrich Louisville, Ky.
Port Neches, Tex.
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-------
Table 18. Use Sites for Styrene and Divinylbenzene Monomer (Cont'd)
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
Goodyear Tire & Rubber Akron, Oh.
Houston, Tex.
Hammond Plastics Worcester, Mass.
Oxford, Mass.
Hatco Polyester Bartow, Fla.
Colton, Calif.
Jacksonville, Ark.
Linden, N.J.
Swan ton, Ohio
Hercules Inc. Clairton, Pa.
Hooker Chem. Corp. North Tonawanda, N.Y.
ICT United States Wilmington, Del.
Interplastic Corp. Jackson, Miss.
Minneapolis, Minn.
Pryor, Okla.
lonac Chem. Birmingham, N.J.
Koppers Co. Bridgeville, Pa.
Richmond, Calif.
Monsanto Addyston, Oh.
Decatur, Ala.
Long Beach, Calif.
Springfield, Mass.
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l-i 01
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4-1 CO
W 2
X
10
G
•H
10
01
p£
CO
§
CO
01
1 1 K
ai I-H 01
C ^. 4J
01 C CO Tl
•H -H >-4 01
•a > 4J
CO 1 01 CO
4-1 a> a h
3 C -H 3
,0 01 T3 4J
>^ ^4 -H CO
rH >, M CO
O 4-1 >-, ti
PL, CO CX3
CO
c
•H
CO
01
V-i
01
4J
CO
01
^!
rH
o
X
X
X
X
X
X
X
X
X
X
X
X
-------
Table 18. Use Sites for Styrene and Dlvinylbenzene Monomer (Cont*d)
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
Monsanto (Cont'd) Muscatine, Iowa
Everett, Mass.
Morton-Norwich Products Ringwood, 111.
Owens-Corning Fiberglas Anderson, S.C.
Valparaiso, Ind.
Phillips Petroleum Borger, Tex.
Polysar Plastics Forest City, N.C.
PPG Industries Circleville, Oh.
Houston, Tex.
Springdale, Pa.
Torrance, Calif.
Pressure Chem. Co. Pittsburg, Pa.
Purex Chem. Co. Bristol, Pa.
Carson, Calif.
Reichhold Chem. Azuza, Calif.
Detroit, Mich.
Elizabeth, N.J.
Grand Junction, Tenn.
Houston, Tex.
Jacksonville, Fla.
Morris, 111.
South San Francisco, Cal.
Tacoma , Wash .
0)
01
1-1
^
1 }
M
>>
.H
0
X
X
X
X
X
X
X
X
CO
c
•H
CO
pel
25
^
CO
td
CO
•"•
X
CO
1 C CU
a) o) a
C 'H ps
4) 73 rH
M id o
>, 4.1 o.
t-i 3 O
co pq o
X
CO
10 M
0) O)
Q) O
4J 4-1
id co
iJ tfl
iH
t£ W
«
CO •«
X
A)
c
0)
N
C M
0) M
1 43 0)
01 rH S
c :>, >,
01 C >H
l-l -H O
>» > ex
4J -H O
w p cj
0)
•O
•H
^1
•a
Jd
G
1 <
cu
c u
01 -rl
U 4J
co i ai co
4-1 U C M
a c -H 3
43 CU T3 4J
Ps r-l 'H IT]
i-H X 1-1 0)
O 4J >, C
(Xi 1/3 {X 9
(0
C
-H
CO
(U
OS
}4
cu
4-1
CO
cu
^
T— 4
O
(X:
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
-------
Table 18. Use Sites for Styrene and Divinylbenzene Monomer (Cont'd)
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
The Richardson Co. Channelview, Tex.
Madison, Conn.
West Haven, Conn.
Rexene (Dart Industries) Holyoke, Mass.
Joliet, 111.
Ludlow, Mass.
Santa Ana, Calif.
Rockwell International Astabula, Oh.
Rohm & Haas Co. Philadelphia, Pa.
Bridgeburg, Pa.
Knoxville, Tenn.
SCM Corp. Chicago, 111.
Cleveland, Oh.
Huron, Oh.
Reading, Pa.
San Francisco, Calif.
Shell Chem. Belpre, Oh.
Leominster, Mass.
A.E. Staley Mfg. Co. Kearney, N.J.
Lemont, 111.
Stepan Chem. Co. Anahiem, Calif.
Solar Chem. Corp. Chattanooga, Tenn.
01
B
01
^
4J
W
r-H
0
P*
X
X
X
X
X
X
X
X
X
X
X
CO
B
•H
M
0)
52
^
CO
1.0
CO
3
X
U)
0) M
1 B W
0) ft) B
B -H £.
01 T3 i-H
t-i to O
X tJ p.
4J 3 O
CO PQ U
W
0) M
Q) 0)
X S
0) 0
4J | *
(0 U
>-) nj
rH
Pd U
PQ
CO >4
X
0)
B
0)
N
B M
0) M
1 .£> 0)
a) 1-1 a
B >. F>
0) B >-l
l-l -H O
>, > D.
U -H O
Cfl O O
X
01
•o
•H
I-J
•a
r;
B
1 <
01
B U
01 -H
M 01
^> >~i
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to S
n
B
•H
in
at
P£
CO
§
X
in
0)
I I X
0) iH 01
C ^> 4J
0) C CO T3
•H -H h4 01
•a > 4J
n) i ai id
4J 01 B VJ
3 C -H 3
XI 01 TJ 4J
>•> »-i -H n)
^< X »-l M
O 4J S*, C
in
C
•H
U)
01
M
O)
i-i
in
0)
^-,
i-i
o
PH
X
X
X
X
X
X
X
X
X
-------
Table 18. Use Sites for Styrene and Divinylbenzene Monomer (Cont'd)
(SRI, 1977; Soder, 1977; Frey, 1976; Chem. Prof., 1977a,b, 1974b)
Southwest Latex Bayport, Tex.
Sterling Plastics Orange, Calif.
Windsor, N.J.
Sybron Corp. Birmingham, N.J.
Haledon, N.J.
Texas Chem. & Plastics Longbeach, Calif.
Texas - U.S. Chem. Port Neches, Tex.
Tylac Chem. Cheswold, Del.
Kensington, Ga.
Union Carbide Bound Brook, N.J.
Marietta, Oh.
Union Oil Co. Charlotte, N.C.
LaMirada, Calif.
U.S. Industries Inc. Copley, Oh.
U.S. Steel Corp. Haverhill, Oh.
Uniroyal Baton Rouge, La.
Scotts Bluff, La.
Vistron Corp. Covington, Ky.
Hawthorne, Calif.
Whit taker Corp. Lenoir, N.C.
Minneapolis, Minn.
0)
c
01
i-i
^
4-1
10
iH
O
X
X
X
X
X
X
X
X
X
(0
c
•H
(0
0)
erf
z
to
-a
CO
PQ
"*
X
X
X
10
01 M
1 B 0)
01 01 B
C -H ?,
Ol TS iH
M nj o
>> 4J ex
4-1 3 O
to « o
X
X
X
X
X
X
(0
CO I-l
0) 01
b£ n
» £>
0) B •-!
M -rl O
^ > cx
4-1 -H O
CO Q O
01
•i-l
M
TJ
f
C
1 4J
cd i o) cd
4J 0) (4 ^
3 C -H 3
JD at -a 4-1
^i ^-l *r4 (T)
iH >^ M (fl
O 4J >, C
PL, CO CX3
V)
c
•H
10
01
^
01
4-1
(A
01
^
r-4
o
^
X
X
X
X
X
-------
Table 19. Tradenames for Various Polymer Products
Polystyrene
Styron (Dow)
Styrofoam (Dow)
Lustrex (Monsanto)
Tuf-Flex (Foster-Grant)
Styropar (BASF Wyandotte)
Helman (U.S. Industries)
Rexene 400 FR1 (Rexene)
Shell 351 (Shell Chem.)
Trycite (Dow)
Pelaspan-Pac (Dox)
ABS Resins
Dow ABS (Dow)
Lustran (Monsanto)
Terluran (ARCQ/Polymers)
Fosta-plus (Foster Grant)
Abson (B.F. Goodrich)
Cycolac (Borg-Warner)
Rexene 500 FR1 (Rexene)
Kralastic (Uniroyal)
Royalite (Uniroyal)
SAN Resins
Tyril (Dow)
Lustran SAN (Monsanto)
Luran (ARCO/Polymers)
Acrylafil (Rexene)
Styrene-Butadiene Copolymers
Dow Latex Series 200-600 (Dow)
K-Resin (Phillips Petroleum)
Amsyn (American Synthetic Rubber)
SBR (Polybutadiene-styrene & latex)
Flosbrene (American Synthetic Rubber)
Copo (Copolymer Rubber & Chem.)
FR-S (Firestone Tire)
Ameripal SBR (B.F. Goodrich)
Plioflex (Goodyear)
Philprene (Phillips Petroleum)
Synpol (Texas-U.S. Chem.)
Styrene-Divinylbenzene Resins
Duolite (Diamond Shamrock)
Dowex (Dow)
Amerlite (Rohm & Haas)
lonac (lonac Chem.)
Polybutadiene-Styrene-Vinylpyridine Latex
Gen-Tac (General Tire)
Chemivic (Goodyear)
Vithane (Goodyear)
Pyratex (Uniroyal)
78
-------
gallons of mixed xylenes (which has a content of 20% ethylbenzene) were used
as industrial solvents (Carlson, 1975). As solvents, mixed xylenes are not
used alone but can be classified as diluents because they are blended with
other solvents. The paint industry consumed nearly half of the solvent mixed
xylenes in 1974 (Carlson, 1975). Mixed xylenes have been used alone in agri-
cultural sprays where they serve as the carrier for the pesticides being applied.
The use of mixed xylenes as an agricultural solvent is expected to decline as
recent regulations require such solvents to have a higher flash point than
xylene (Carlson, 1975). Isolated mixed xylenes are also blended into gasoline.
b. Styrene
As explained in Section II. A. 5. a., styrene is a contam-
inant by-product in pyrolysis gasoline produced when paraffins, condensates,
naphtha, and gas oil are cracked with the intention of producing ethylene.
This pyrolysis gasoline is blended into gasoline and fuel oils, depending upon
composition.
4. Projected or Proposed Uses
The patent literature contains numerous patents describing the
use of styrene, a-methylstyrene, and divinylbenzene in polymer products. Which
particular polymers may become commercially important in the future cannot be
projected at this time. However, because of the polymerization characteristics
of these chemicals, especially styrene and divinylbenzene, it is unlikely that
any large scale application will be developed which does not involve polymer-
ization.
5. Alternatives to Use
Because most of the ethylbenzene which is commercially produced
is used to make styrene, an alternative to ethylbenzene use would require that
79
-------
styrene be made from some ntl.er chemical process. Such a process has been
proposed. A recent patent (U.S. 3,965,206) to Monsanto proposes production of
styrene from toluene and ethylene via stilbene. Basic process evaluations
suggest the economics for this process are quite promising compared to ethyl-
benzene routes (Soder, 1977).
Virtually all of the styrene, ct-methylstyrene, and divinylbenzene
produced is used to make polymer products such as plastics, synthetic rubbers,
and latexes. It may be theoretically possible to state that most uses of these
polymer products could be substituted by an alternative product. For example,
from Table 16, it can be seen that about 20% of the annual styrene consumption
is used in packaging products; alternatives, such as paper products, could be
substituted for this use. Additionally, all of the styrene polymers used to
make plastics for appliances, housewares, toys, and automobiles could be sub-
stituted by glasses and metals. However, styrene products are used for reasons
of economics, safety, and convenience and, therefore, may be difficult to
replace.
C. Entry Into the Environment
1. Points of Entry
a. Production
Sources of emissions from styrene production have been
examined by Pervier ££ al. (1974). Styrene emissions can result from vents on
distillation columns and other process equipment, storage tank losses, miscell-
aneous leaks and spills, process wastewaters, and solid process wastes. Similar
points of release can probably be applied to production of ethylbenzene,
a-methylstyrene, and divinylbenzene.
80
-------
The severity of losses from production varies from plant
to plant; however, according to Pervier e_t al. (1974), emissions from styrene
production are low in comparison to other petrochemical industries which have
been surveyed. Fuller e_£ al. (1976) have estimated the production losses
from ethylbenzene to be 1%. An EPA funded study by Hydroscience (Contract
68-02-2577) of ethylbenzene plants has suggested a much lower figure. The
accuracy of these estimates is not known.
b. Use
Styrene, a-methylstyrene, and divinylbenzene are basically
used in polymer production. Pervier e_t al. (1974) indicate that styrene can
be emitted from polymerization processes from dryer vents, from some waste-
water and solid wastes, and from some fugitive emissions from reactors. Other
losses could result from various leaks and spills. Fj elds tad e_t_ al^. (1979)
and Pfaffli et al. (1979) have both shown that considerable amounts of styrene
(50-150 ppm) and styrene oxide (0.03 - 0.2 ppm) can be detected in polyester
fabrication plants and therefore losses to the environment also seem likely.
The styrene oxide is thought to be produced by the peroxide curing agent.
Relatively small amounts of ethylbenzene are used for
solvent purposes as compared to amounts used to manufacture styrene. However,
in these uses, substantial quantities of ethylbenzene may be allowed to vaporize
from exposure to air. The nature of the use will probably determine the
potential for emission.
c. By-Product or Contaminant
As mentioned in Section II. A. 5, ethylbenzene is produced
as a by-product in catalytic reformate and pyrolysis gasoline. Styrene is also
a by-product in pyrolysis gasoline. The processes which produce catalytic
81
-------
reformate and pyrolysis gasoline are general petrochemical operations which
have the potential to make emissions from distillation column or process equip-
ment vents, and from leaks, spills, etc. These process emission sources are
probably quite small, however, as compared to emission potential from use of
the catalytic reformate chemicals. Large quantities of these chemicals are
blended into gasolines. Stavinoha and Newman (1972) and Sanders and Maynard
(1968) have determined amounts of ethylbenzene in motor gasolines in volume
and weight amounts up to 3%. It is possible that significant amounts of
ethylbenzene are emitted from gasoline when vapors escape from filling an
automobile with gasoline at a service station.
d. Miscellaneous Disposal
Grossman (1970) has detailed an example of unique styrene
release to the environment in Connecticut. During construction of a residential
development in Gales Ferry, Connecticut, waste styrene had been used to burn
brush in clearing land because of the intense heat generated when styrene
undergoes combustion. At least two leftover drums of styrene, partially filled,
were buried beneath one to four feet of fill at two separate places at
Gales Ferry. Within several years, the new residents at Gales Ferry noticed
contamination of well water; it was identified as styrene. The buried drums
of styrene were removed from the area but styrene contamination in the water
persisted at a declining rate for two years. Grossman (1970) concluded that
the styrene contamination from the buried drums was due to the unique geological
make-up of the area.
e. Monomer Migration from Polystyrene
As mentioned in Section II. B. 1. b, a small percentage of
styrene monomer is present in finished polystyrene products. Davies (1974)
82
-------
has monitored styrene migration from polystyrene packaging materials into
food. The rate of migration is apparently dependent upon monomer concentration,
temperature, food type, and other parameters.
2. Emission and Effluent Control Methods
Pervier et^ al. (1974) briefly discuss the pollution and emission
control methods used by the styrene manufacturing industry. Emissions from
vents, such as distillation columns, are normally channelled through some kind
of condensible vapor conservation system to recover valuable products for
recycle or use. Some vent emissions can be burned as fuels for process opera-
tions. Solid process wastes, such as spent catalyst and filter aids, are
usually disposed to sanitary landfills. About 500 pounds of catalyst are
disposed of for every million pounds of styrene product. Spilled materials
are normally disposed to landfills also.
Process wastewaters are normally sent to on-site treatment
lagoons. Treatment varies from plant to plant, but usually includes neutral-
ization and filtration. Varying degrees of process wastewaters, both treated
and untreated, can be recycled. One petrochemical plant's five-day lagoon
effluent was monitored to have a styrene concentration of 0.03 ing/liter
(Webb e£ al., 1973).
It is judged that similar emission controls and methods are
utilized by ethylbenzene, a-methylstyrene, and divinylbenzene manufacturers.
Users of styrene have had styrene detected in their wastewaters.
A synthetic rubber plant's settling pond contained a styrene level of 0.003 mg/
liter (Webb et_ al., 1973).
83
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3. Production in the Environment
a. Motor Vehicle Exhausts
Table 20 lists the representative volume compositions of
hydrocarbon components of vehicular emissions which Schofield (1974) obtained
from General Motors Laboratories. It can be seen from Table 20 that ethyl-
benzene is present in vehicle exhausts as well as some styrene. The EPA
estimated that in 1974, about 12.5 million tons of hydrocarbons were emitted
by motor vehicles (Council on Environmental Quality, 1975). If it is assumed
that the average volume composition of all vehicular emissions is 0.60% ethyl-
benzene, then it can be calculated that roughly 280 million pounds of ethyl-
benzene are emitted per year from motor vehicle exhausts. This is equivalent
to about 4% of the total amount of ethylbenzene manufactured industrially each
year. Similar but less quantitative estimates can be calculated for styrene
(styrene value is combined with £-xylene value).
b. Combustion Systems
Styrene has been detected in hydrocarbon exhausts from
spark-ignition engines utilizing specific fuel types (Fleming, 1970). Fleming
(1970) identified styrene in exhausts from fuel compositions containing large
quantities of m-xylene; Fleming (1970) additionally showed that exhaust compo-
sitions from spark-ignition engines are dependent upon aromatics in the fuel.
Styrene and methylstyrenes have also been identified in
oxy-acetylene and oxy-ethylene flames (Crittenden and Long, 1976). It is
possible, therefore, that styrene may be emitted from motor vehicle exhausts
as well as various combustion systems.
84
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Table 20. Representative Volume Compositions of Hydrocarbon
Component of Vehicular Emissions (Schofield, 1974)
Methane
Acetylene
Ethylene
Propylene
Toluene
1-Butene, 1,3-butadlene
Benzene
Ethane
3 Ethyl pentane, 2,2,4-trimethyl pentane
Isopentane
n-Butane, 2,2-dimethyl propane
2,3- and 3,3-Dimethyl hexane, 2,3,3-
and 2,3,4-trimethyl pentane
p,m-Xylene
Propadiene
o-Xylene, phenyl ethylene (styrene)
cis-1-Phenyl-l-propene, t-butyl benzene,
1,2,4-trimethyl benzene
2,3-Dimethyl pentane, 2-methyl hexane
2-Methyl pentane
1-Methyl 3- or 4-ethyl benzene
Ethyl benzene
cis-2-Butene
l-Methyl-2-ethyl benzene, 2-phenyl-l-propene
2,4-Dimethyl pentane, 2,2,3-trimethyl butane
Other paraffins
Other aromatics
Other olefins
Reciprocating
Engine, %
24.27
17.51
14.12
7.34
5.97
4.07
2.15
1.97
1.81
1.73
1.59
1.54
1.30
1.00
0.76
0.76
0.64
0.55
0.52
0.51
0.51
0.45
0.38
4.07
1.11
3.37
Rotary
Engine, %
4.88
3.30
8.09
5.34
16.34
2.99
1.31
1.32
2.89
8.64
4.51
2.73
5.57
0.95
2.67
2.45
2.86
1.36
2.31
1.67
0.25
1.07
1.32
6.26
3.78
5.11
85
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c. Pyrolysis
Fisher and Neerman (1966) have identified styrene in gas
products from laboratory pyrolysis of phenolic resins used in commercial brake
linings for automobiles. In this study to determine compositions of brake
lining resins, various resin samples were subjected to temperatures reaching
1100°C by a laboratory pyrolyzer to convert the solid samples into gaseous
products which could be analyzed by gas chromatography. Detectable amounts of
styrene were identified in all pyrolyzed samples.
It has been reported that brake linings in automobiles
can be subject to temperatures of 800 to 1000°C (Rohl e£ al., 1976). Under
these conditions, it may be possible that small amounts of styrene are produced
and thereby, emitted to the general environment.
d. Cigarette Smoke
Both ethylbenzene and styrene have been identified in
cigarette smoke condensate. Johnstone et al. (1962) detected ethylbenzene in
cigarette smoke in yields ranging from 7 to 20 micrograms per cigarette as well
as styrene, in combination with o_-xylene, in yields ranging from 20 to 48
micrograms per cigarette.
e. Incineration
It was previously mentioned that pyrolysis of phenolic
resins can produce styrene. It is possible that municiple incineration of
phenolic type resins could emit styrene. It is also conceivable that inciner-
ation of the many types of styrene polymers could release styrene to the
environment.
86
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D. Analytical Methods
1. Sampling Techniques
Analytical methods have been developed for styrene and related
compounds when present in solid, liquid, or gaseous substrates. The solid
substrates for which there exists a significant body of literature are
polystyrene and rubber samples. Sampling is relatively straightforward for
solids, but more complicated for gases and liquids. The liquid substrate of
greatest concern for styrene sampling is water. Recently reported techniques
for the extraction of styrene from water are discussed below. Most of the
environmental monitoring of styrene compounds has been done on the atmosphere,
the ideal environmental medium for the containment and transport of appreciable
quantities of these compounds since all the compounds are relatively volatile.
In addition to the importance of air sampling as a primary method for monitor-
ing styrene compounds in the environment, it presents certain special problems
of recovery, particularly when quantitative estimates are required.
Sampling techniques are to a great extent independent of the
particular analytical technique employed for determining the sample. The
sampling techniques discussed in this section are therefore all generally
applicable to the analytical methods in the sections which follow.
There is a much larger body of literature on sampling and
analytical techniques for styrene and ethylbenzene than for divinylbenzene
and a-methylstyrene. Nevertheless, the chemical and physical similarities
between styrene and the other styrene monomers suggests that the sampling and
analytical techniques discussed below are in most cases equally applicable,
and in the balance directly adaptable to all of the styrene monomers.
87
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Some of the earliest methods for sampling styrene in air were
developed by Rowe et_ a.L. (1943) and were cited years later (Boundy and Boyer,
1952; Dow Chemical, 1960) as the basis for improved collection methods. The
first of these is designed for small samples. A bead-packed absorber (see
Fig. 9) filled with a suitable styrene solvent is immersed in a cold bath and
the measured air sample (approximately 1 liter) is passed through it. For
large samples a reflux cold trap can be used (Boundy and Boyer, 1952). This
consists of a fritted glass absorber cooled by circulating around it a mixture
of carbon tetrachloride and chloroform refrigerated in a dry ice bath. A
third collection method, useful for spot samples of air, utilizes an evacuated
flask from which styrene may be recovered with an appropriate solvent.
Techniques similar to these have been employed more recently. For example,
Neligan e£ al. (1965), in monitoring the atmosphere of Los Angeles for
hydrocarbons, including styrene and ethylbenzene, collected samples in
plastic bags and then transferred the samples to evacuated 2 liter glass
flasks. Yamamoto and Cook (1968) used a conventional all glass fritted
bubbler to monitor styrene and ethylbenzene in air. Recovery efficiency of
the styrene for concentrations within 25 to 200 ppm was within 95 to 100%,
but the recovery for ethylbenzene over the same concentration range was 64
to 92%.
For qualitative analysis of air, a variety of adsorbents and
solvents are suitable for retaining styrene monomers and ethylbenzene. Quanti-
tative analysis of the highest accuracy where ultratrace conditions are
encountered presents a different situation. Grob and Grob (1971) assert that
only charcoal filters with liquid desorption is satisfactory for ultratrace
work, as these alone are capable of controlled adsorption independent of
88
-------
'if
mr
d
/
i
JSP
_ /• 0 0 TUIINt
/
>— (// 0 0. TUBING
'>OCO WITH
y — V*lw. CLASS
' IC10I
Figure 9. Bead-Packed Absorber for Absorbing Styrene Monomer from Air
(Boundy and Boyer, 1952)
89
-------
humidity, and full recovery without contamination by material from the absorbed
medium. The design of a charcoal based sampling system is shown in Figure 10.
Each charcoal filter is made of 25 mg wood charcoal. The simple construction
allows excellent replication of characteristics from one filter to another.
The filter holder shown in Figure 10 is connected to a water pump with the air
flow adjusted to 2.5 ml/min by means of a needle valve. The sample is recovered
in a very low volume (ca. 0.3-0.5 ml) of carbon disulfide in the apparatus
shown in Figure 11.
Activated charcoal was used by Cooper e£ al. (1971) to trap
ethylbenzene in ambient air in an industrial environment, and by Parkes e£ al.
(1976) for trapping styrene in ambient air. In the latter case, with carbon
disulfide desorption, 40 ppb styrene in a 10 liter air sample -(sampled at
200 ml/min) could be recovered with 100% efficiency.
Kalliokoski and Pfaffli (1975) developed a personal sampler
consisting of batteries, pump, and a charcoal trap which is worn by a worker.
Air from the worker's breathing zone is sucked through a tube into a charcoal
filter. Recovery is with dimethylformamide. The range and sensitivity of the
system is 5 to 1500 ppm for one hour of sampling at 0.2 £/min; for a four hour
sampling period at the same rate, the range is 2 to 400 ppm. Sample recovery
from air with known concentrations of styrene was better than 90%. Measurement
of the air flow rate proved to be the greatest source of error.
Cold trap preconcentration of air samples is a popular method
of analyzing styrenes and ethylbenzene in ambient air samples where concentra-
tions less than 1 ppb are found. A glass bead cold trap (liquid nitrogen) was
used by Lonneman et^ al. (1968). After collection the sample was directly
flushed into a gas chroraatograph. Concentrations well below 6 ppb could be
90
-------
i •- T
r*>
/- • • •••• \
3-glass tube
ID. 4.5 mm
3 O.D. 6.0 mm
stairless-steel' \ "shrmkable Teflon
screen charcoa.
to water pump
silicone rubber
0-ring
. second filter
• Teflon fitting
first filter
glass fibre
"dust filter
air inlet
Figure 10. Design of Charcoal Filter and Filter Holder Containing Two Charcoal
Filters in Series (Grob and Grob, 1971)
91
-------
cold water in
}(]• -- cold wafer out
II
--' cold finger
.perforated
I Teflon fitting
-•charcoal
filler
5-mi flask
Figure 11. Glass Apparatus Allowing Continuous Extraction of Charcoal Filters
Using a Very Low Volume of Solvent (Grob and Grob, 1971)
92
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detected. Neligan et al. (1965) also concentrated their samples with a fire-
brick cold trap. A similar heat desorption technique was used by Parkes &t^ al.
(1976) with a carbon adsorbent. They were able to measure down to 1 ppb with
styrene and 4 ppb with ethylbenzene.
In Sweden, personnel and ambient air samples containing styrene and styrene
oxide were collected by adsorption in charcoal (Fjeldstadt et al., 1979; Pfaffli
et al., 1979). The samples were then eluted with carbon disulfide or dichloro-
methane.
Carbon filters have also been used to sample styrene in water
(Gordon and Goodley, 1971). Extraction of water samples with organic solvents
such as chloroform, ether, or hexane is an alternative to charcoal filtration.
Austern et al. (1975) extracted water samples with Freon-TF and were able to
detect minimum levels of styrene at 0.5 and 0.3 ng respectively per water sample.
Styrene and other hydrocarbons can be removed from water samples
by adsorption on macroreticular resins followed by solvent elution. Recovery
is said to be excellent at ultra low levels (Bertsch et^ al., 1975).
Gas phase stripping is a relatively new method (Grob and Zuercher,
1976) in which a gas is bubbled through a water sample and volatile chemicals
are collected on an adsorbent (wood charcoal, heat activated). It is possible
to recover 0.5 ppb ethylbenzene from a liter of tap water using this technique
with an extraction efficiency of 99.4% using methylene chloride as the solvent
desorbent.
Table 21 summarizes the air and water sampling methods above.
2. Chromatographic Methods
Gas chromatography is the single most effective tool currently
available for the separation of complex mixtures of organic compounds (Gordon
93
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Table 21. Sampling Methods for Styrene Monomers and Ethylbenzene
Method
Medium Sampled
Recovery/Efficiency
Reference
Bead-packed absorber air
Class bead cold trap air
Reflux cold trap air
Ambient bubbler air
Evacuated container air
Plastic bag air
Carbon filter air
Carbon filter air
Carbon filter/solvent desnrption air
Carbon filter/heat desorption air
Carbon filter water
Solvent extraction water
Macroreticular resins water
Cas phase stripping water
measure concentrations less
than 6 ppb
25-200 ppm styrene/95-100%
25-200 ppm ethylbenzene/64-92%
40 ppb styrene/100%
0.5 ng styrene/sample
0.3 ng ethylbenzene/sample
0.5 ppb ethylbenzene/99.3%
Roundy and Boyer, 1952
Lonneman et al., 1968
Boundy and Boyer, 1952
Yamamoto and Cook, 1968
Boundy and Boyer, 1952
Neligan et_ al. , 1965
Crob and Grob, 1971
Cooper ejt^ al. , 1971
Fjeldstad e£ al., 1979
Pfaffli et_ a±., 1979
Parkes e£ al., 1976
Gordon and GoodJey, 1971
Austern et^ aj^ , 1975
Bertsch £t^ al^ , 1975
Grob and Zuercher, 3976
-------
and Goodley, 1971). It is also the most common tool mentioned in the litera-
ture for determining styrene and ethylbenzene in the air and water samples as
well as residual amounts of styrene in polymers.
A typical example of routine gas chromatography applied to
ethylbenzene monitoring was a study of the Los Angeles atmosphere by Altshuller
and Bellar (1963). Ethylbenzene was detected in the air samples by directly
injecting 3.12 ml of air into a gas chromatograph equipped with a flame ionization
detector. Concentrations down to 0.005 ppm were measured. The lower limit of
sensitivity of the apparatus was not given.
Neligan £jt al. (1965) also monitored the Los Angeles area atmos-
phere, performing analyses with a modified flame ionization gas chromatograph
using a copper capillary coated column. Extensive sample preparation included
drying with Ascarite, freeze-out trap collection at liquid oxygen temperatures,
and rapid vaporization prior to injection. Recovery of hydrocarbons from
spiked air was reproducible within +10% at the 0.1 ppm level and +25% at the
0.001 ppm level. Ethylbenzene and styrene were detected along with 18 other
aromatics in air samples analyzed. Fjeldstad £t al. (1979) and Pfaffli ejt al.
(1979) both used gas chromatography flame ionization detection for detection
of styrene and styrene oxide in charcoal collected samples taken around plastics
industries using styrene monomer. PfSffli et al. (1979) used a capillary column
and confirmed the qualitative results with GC-MS. The detection limits for the
two studies were around 3 ppb.
Ethylbenzene was detected in the atmosphere over Zurich,
Switzerland in an application of ultratrace analysis on capillary columns via
gas-liquid chromatography/mass spectrometry (Grob and Grob, 1971). Samples
were collected using the charcoal filters described in the previous section
95
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(see Fig. 10). These were extracted with carbon disulfide and analyzed with
specially modified gas chromatography columns, followed by mass spectrometry.
It was shown'that charcoal does not attain a stable equilibrium in prolonged
contact with the atmosphere. Less volatile substances are capable of replacing
the more volatile substances on prolonged exposure of filters to air. Conse-
quently there is an optimum exposure time for charcoal filters for maximum
sample retention. Ethylbenzene concentration in Zurich air was 8.7 ppb. No
lower limit of detection was given, but similar molecules were detected at much
lower levels (e.g., ethyldimethylbenzene at 0.95 ppb). A further refined system
(again using gas-liquid chromatography/mass spectrometry) was able to detect
hundreds of hydrocarbons up to C., in Zurich tap water after they were stripped
from water onto an adsorbent (Grob, 1973). The lower limit of sensitivity was
found to be 0.1 ppt. Routine assays on the order of 5 ppt are possible with
errors on the order of 25%. Errors tend to be on the low side due to failure
to recover all of the sample from the collector (Grob, 1973).
Bergert et al. (1974) developed another ultratrace system
employing gas chromatography/mass spectrometry which was used to analyze ambient
air collected in Frankfurt-am-Main, Germany, for hydrocarbons, including ethyl-
benzene. A microgradient tube is used for enrichment of the components.
Separation is carried out on glass thin-film open tubular columns by means of
linear-programmed low temperature gas chromatography. Combined with mass
spectrometry, this system can detect components down to 0.02 ppb, but the
usual range of operation is 0.1 ppb to 1.0 ppm.
Louw and Richards (1975) reported a gas chromatography/infrared
spectroscopy system for low molecular weight hydrocarbons. Each sample com-
ponent is identified in five to six minute intervals. Approximately 14-19 wg
96
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of each hydrocarbon component must be present per sample. At the time of publi-
cation of the method, however, it had not yet been tested with actual urban air
samples.
In addition to air pollution monitoring, gas chromatography has
been used to determine styrene, ethylbenzene, and other organics in water.
Austern £t al. (1975) developed a method for extracting wastewater samples with
Freon-TF, then used standard gas chromatographic techniques to show the extrac-
tion technique is capable of recovering approximately 99% of styrene and
ethylbenzene when these are present in concentrations of about 0.25 mg/H .
Gas chromatography was also used to detect ethylbenzene and
styrene in commercial deionized charcoal-filtered water by first air stripping
the organics, collecting them on a solid polyphenyl ether adsorbent, and then
thermally stripping them onto a capillary column (Dowty et^ al., 1975). In
this case the gas chromatography was followed by mass spectrometry in a com-
puter controlled system for identification and quantification of organics in
water. Concentration of ethylbenzene and styrene were not reported.
Bertsch et al. (1975) used a system similar to Grob and Grob
(1971) to sample ethylbenzene in river water. Although quantitative data were
not presented, it can be inferred the apparatus is capable of ultratrace
analysis to the ppb level.
Parkes e_t al. (1976) used a relatively simple charcoal adsorp-
tion/heat desorption technique to concentrate organics in air and determine
them via flame ionization gas chromatography. Heat desorption was accomplished
with a Bendix Flasher which rapidly heats the sample trap from ambient to
several hundred degrees, volatilizing the organics. Parts per billion sensi-
tivities are easily achieved with this method with a total analysis time of
about 20 to 40 minutes per sample.
97
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Hoshika (1977) reported a gas chromatography method which does
not require preconcentration of the samples, even when the styrene is at the
ppb level (which is too low for flame ionization detection without preconcen-
tration) . The styrene is converted to styrene dibromide by reacting it with
bromine. The dibromide is detected with an electron capture detector. The
electron capture system was shown to be 500 times more sensitive to styrene
bromide than a flame ionization system to styrene. Of 138 compounds tested
for interference effects on the bromination of styrene, all except six com-
pounds proved to have negligible effect (error < 5%). The six and the respec-
tive % errors introduced into the height of the styrene dibromide chromato-
graphic peak were 1-nonene (19%), 1-dodecene (100%), £-cresol (150%), m-cresol
(45%), 2,3-xylenol (20%), and 3,5-xylenol (20%). The phenolic compounds could
be removed with base. Recovery of the styrene from air samples spiked with
13 ppb styrene was about 90%. The range of the styrene detected in urban air
samples was 0.1 to 0.4 ppb.
Reichel et al. (1977) used gas chromatography/mass spectrometry
to determine polychlorinated styrenes (octachloro and possibly also hexa and
heptachlorostyrenes) in heron tissues. This routine application of GC/mass
spectrometry achieved a sensitivity of at least 0.01 ppm.
The requirement for the high sensitivities exhibited by the
previously described systems does not exist for assays designed to detect
styrene monomers in polymer substrates. Thus, Shapras and Claver (1964)
determined styrene and ethylbenzene in various styrene polymers and copolymers
using gas chromatography with a hydrogen flame detector, reporting a sensi-
tivity of 10 ppm monomer in the polymer. Esposito and Swann (1965) developed
a technique for the determination of styrene monomer in polyester resins by
98
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gas-liquid chromatography. The styrene monomer is used as a consolidating
agent in the resins; regulation of styrene concentration is important in
determining the properties of the resin product. The procedure has good
precision for styrene resins in at least the concentration range of 12 to 47%.
It is not relevant to environmental monitoring. Haken and McKay (1966) re-
ported another procedure for styrene in polyester resins via gas chromatog-
raphy. No sensitivity data was given.
Table 22 summarizes the chromatographic analytical methods for
styrene described above.
3. Spectroscopic Methods
Analytical methods employing ultraviolet spectroscopy (without
gas chromatography) were primarily developed for determining styrene monomers
in polymer products. The spectroscopic method developed by Yamamoto and Cook
(1968), however, was for styrene in air. Spectroscopic methods are rapid and
require a minimum amount of apparatus. However, they cannot compete with the
sensitivity achievable with gas chromatography. Also, ultraviolet methods
usually cannot distinguish between various volatile substances in polystyrene
when more than one is present, such as other copolymers or stabilizers (Crompton
et al., 1965).
Some UV methods depend on the fact that the unsaturated side
chain of styrene causes an absorption below 260 my while polystyrene has an
absorption above 260 nm. In these cases a solvent must be chosen which will
dissolve both the monomer and polymer. Murphy and Forrette (1961) avoided this
problem by extracting styrene from polystyrene with cyclohexane then measuring
the monomer at 250 nm. Data on the sensitivity and concentration range of the
method were not given. A similar method (Rose, 1965) is said to be able to
99
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Table 22- Chromatographic Analytical Methods for Styrene Monomers and Ethylbenzene
Method
Compound(s)
Source
Sensitivity Reference
Gas Chromatography-FT (direct injection)
Gas Chromatography - FT
Gas Chroraatography-FI (cold trap)
Gas Chroraatography
Gas Chromatography - FT
Gas Chromotography-FI
o Gas Chromotography-FI (also GC-MS)
Gas Chromatography - EC
Gas/Liquid Chromatography
Gas/Liquid Chromatography/Mass
Spectroscopy
Gas Chromatography/Infrared Spectroscopy
Gas Chromatography/Mass Spectroscopy
ethylbenzene
ethylbenzene,
styrene
ethylbenzene,
styrene
styrene
styrene
styrene
styrene oxide
styrene
styrene oxide
styrene as
the dibromide
styrene
ethylbenzene
ethylbenzene
ethylbenzene
ethylbenzene
polychlorinated
styrenes
atmosphere >0.005 ppm Altshuller and Bellar, 1963
styrene polymer >10 ppm Shapras and Claver, 1964
atmosphere
>0.01 ppm Neligan ejt a}_. , 1965
polyester resins ND Ilaken and McKay, 1966
* 0.2 ppb Parkes ejt a.1. , 1976
atmosphere 3 ppb Fjeldstad et al., 1979
atmosphere
<40 ppb
PfSffli et al., 1979
atmosphere 0.1 ppb Hoshika, 1977
polyester resins ND Ksposito and Swann, 1965
atmosphere
potable water
atmosphere
heron tissue
>1 ppb Grob and Crob, 1971
M).l ppt Grob, 1973
ND Louw and Richards, 3975
0.02 ppb Bergert et_ a±, J974
>0.0l ppm Reichel £t a_K , 1977
* Method developed with synthetic mixtures of air and hydrocarbons, but applicable to atmospheric monitoring.
ND No data reported.
-------
detect as little as 0.02% monomer in food grade polystyrene. Apart from what
may be a safe level of monomer in polymers used for food packaging, levels of
styrene monomer above 0.25% may impart a definite odor to foods (de Forero &t_
al., 1971).
Yamamoto and Cook (1968) extracted styrene and ethylbenzene
from air samples by drawing them through spectro-grade octane. The styrene in
the samples was directly determined by UV spectroscopy at 268 nm and ethyl-
benzene at 291 nm. These wavelengths were chosen for minimal (or at least
compensable) cross interference between the two compounds. Tested with spiked
samples, the method proved capable of determining styrene at levels of 25 to
200 ppm with about 95% efficiency or better (including extraction). Ethyl-
benzene reproducibility was not as good, with efficiency of the method for
ethylbenzene ranging nonlinearly from 65 to 92% over the same concentration
range. Styrene interfered significantly with the ethylbenzene when the
concentration of the ethylbenzene fell below half that of the styrene. The
method can detect styrene and ethylbenzene concentrations as low as 1 ppm.
4. Electrochemical and Miscellaneous Methods
Although the polarography of styrene was investigated in the
early 1940*s, interest in this technique for analysis of styrene took time to
develop. Ragelis and Gajan (1962) extracted styrene from polystyrene resin,
then used polarography to determine the styrene. Their results agreed well
with gas chromatography analyses of the same samples. Sensitivity data was
not given, but Crompton and Buckley (1965) reported sensitivities as low as
20 ppm in the determination of styrene in styrene-acrylonitrile copolymers via
polarography. Results of the polarographic method agreed well with those of
UV spectroscopy at 292 nm.
101
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Using the effect of organic impurities on the double layer
capacitance of an electrode, Formaro and Trasatti (1968) were able to detect
as little as 0.03 ppm of organic impurities in water. Among the compounds
present was styrene. The method, however, is nonspecific. It gives a measure
of the total organic impurities present. It is applicable to industrial
wastewater quality control as well as to tap water monitoring for organic
pollution.
Blake and Rose (1960) described a colorimetric method for
styrene and toluene in air samples. A bulb is inflated with the air to be
tested. Styrene in the sample reacts with an 89.5% solution of sulfuric acid
producing a colored solution. The sample bulb is inflated as many times
(between 3 - 10) as necessary until the reagent solution is the same color as
a standard solution. The concentration of styrene in the sample is propor-
tional to the number of inflations required. The test is very rapid, but
limited in range and sensitivity (approximately 50 to 170 ppm). It is never-
theless suitable for spot checks in enclosed areas with the potential for
undesirably high styrene levels. A similar method for homologs of benzene was
described by Belvedere and Metrico (1967), but this method is not highly
specific for styrene; sensitivity data was not given.
The classical chemical method for styrene was the nitration
method (Boundy and Boyer, 1952). The monomer, which was collected in a bead-
packed absorber, is nitrated with a mixture of concentrated sulfuric and
nitric acids after removal of butadiene (if present) by heating. The nitrated
product is diluted to volume with water and determined by measuring the color
of the solution with a photoelectric colorimeter. This method is suitable for
samples containing styrene in the presence of acrylonitrile, water, butadiene,
102
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ethylbenzene, and benzene. Its accuracy is +15 mg (roughly 1000 ppm).
Methylstyrenes, divinylbenzenes, and other compounds with unsaturated side
chains and which are less volatile than styrene would interfere.
A recent titrametric method for styrene (Roy, 1977) comes
closest of the chemical methods to suitability for trace analysis of styrene.
Its sensitivity is about 5 ppm. The monomer is extracted from styrene-acrylo-
nitrile polymer with benzene, then brominated under conditions which do not
favor bromination of the less active double bond of acrylonitrile (the two
compounds may thus be determined in the presence of each other). The results
for the determination of styrene monomer in styrene-acrylonitrile polymer
samples which contained about 1% monomer agreed very well with infrared analy-
ses for styrene on the same samples.
E. Monitoring
1. The Atmosphere
Styrene and ethylbenzene have been monitored in the atmosphere
over the west coast of the United States, and also in Europe and Japan.
Ethylbenzene is apparently more prominent in the atmosphere than styrene; it
has been determined more frequently and in higher concentrations than styrene
in all of the following studies.
In a survey done in September 1961, Altshuller and Bellar
(1963) found approximately 0.01 ppm ethylbenzene in the air over Los Angeles,
California. The total aromatic concentration was approximately an order of
magnitude greater; therefore, the ethylbenzene represented about 10% of the
total aromatic compounds detected in the air, and roughly 1% of the total
carbon compounds detected. The authors noted that only a small number of the
compounds detected are active in smog-producing reactions, the majority being
103
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inert to such reactions. The total concentration of aromatic compounds in the
Los Angeles air had not changed five years later when a new study was under-
taken by Lonneman e£ al. (1968). The ethylbenzene concentration averaged
0.006 ppm in the more recent study (with the highest measured concentration of
ethylbenzene at 0.022 ppm), indicating that its concentration (like that of
the total aromatics) did not change significantly over that five year period
of time. (The most abundant aromatic detected was toluene. At 0.04 ppm,
toluene was twice as abundant as benzene or jn-xylene, the two compounds which
immediately followed toluene in abundance.) The ethylbenzene concentrations
reported by Lonneman e_t al. (1968) and Altshuller and Bellar (1963) agree also
with the data of Neligan et_ al. (1965) who monitored five different sites in
California (see Table 23), including Los Angeles, reporting an average of
0.01 ppm ethylbenzene. The Neligan group also detected styrene at four of
these sites (see Table 23) at an average concentration of 0.005 ppm. The
reproducibility of the analytical procedure was + 25 percent at 0.001 ppm. If
there was any styrene in the air at Los Angeles, it was below the limit of
detection (0.0005 ppm).
Grob and Grob (1971) found 8.7 ppb ethylbenzene in the air in
Zurich, Switzerland. Styrene was not detected. The lowest concentration of
any of the other detected hydrocarbons was 0.74 ppb for ethyldimethylbenzene.
Toluene was not only the most abundant of the aromatics, but, at 39 ppb, also
the most abundant hydrocarbon of all those detected. The authors noted the
striking resemblance of the kinds of compounds detected and their relative
abundance in the composition of gasoline. The alkanes in air were slightly
reduced in concentration compared to the aromatics over what one would expect
for gasoline.
104
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Table 23. Styrene and Ethylbenzene Concentrations (ppm V/V) in California Air Samples
(Neligan e£ arl. , 1965)
Inglewood Long Beach Burbank Azusa Los Angeles
Time (PST) 0700 0730 0700 0730 0600 0900 0900 1000 0600 0700
Styrene 0.008 0.015 0.002 0.001 0.002 0.003 0.004 0.005 not detectable
Ethylbenzene 0.011 0.013 0.006 0.012 0.005 0.008 0.004 0.004 0.014 0.015
-------
In November 1973, ethylbenzene was detected in the air of
Frankfurt-am-Main, Germany (Bergert ejt al., 1974) at roughly 1 ppb. More than
twenty other hydrocarbons were monitored at the same time. Styrene also has
been found in urban air in Japan at a concentration of 0.2 ppb (Hoshika,
1977). It is possible that Neligan et: a_l. (1965) would have detected styrene
at about this concentration in Los Angeles if their analytical method had been
sufficiently sensitive.
Olivo e£ al. (1973) have shown that industrial activity may
contribute to styrene contamination of the atmosphere. The working areas of a
plastics plant in Italy were monitored. Styrene concentration in the air of
molding rooms frequently exceeded the maximum allowable concentrations.
Pervier e_t al. (1974) note that although styrene has been monitored in the
vent emissions of petrochemical plants in this country, the quantities in-
volved are not significant compared to other polluting processes (see Sec-
tion II-C for a discussion of the environmental contamination potential of
styrene). Two Swedish studies have detected considerable concentrations of
styrene and styrene oxide in air samples collected at polyester resin plants
(fiber glass lamination). Concentrations of 50-150 ppm styrene and 0.03 -
0.2 ppm styrene oxide were detected (PfSffli £t al., 1979; Fjeldstad et al. ,
1979).
In summary, the available data from the West Coast, Switzerland,
Germany, and Japan indicates that ethylbenzene is significantly more abundant
than styrene in the atmosphere. While industrial processes may be one source
of these compounds, the suggestion has been raised that their presence might
also be attributable to the widespread use of gasoline (see Table 20). Table
24 summarizes the atmospheric monitoring data for styrene and ethylbenzene.
106
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Table 24. Atmospheric Monitoring Data for Styrene and Ethylbenzene
Compound
Location
Approximate
Average Concentration
Reference
Styrene California
Styrene Urban air (Japan)
Ethylbenzene Los Angeles, California
Ethylbenzene Los Angeles, California
*
Ethylbenzene California
Ethylbenzene Zurich, Switzerland
Ethylbenzene Frankfurt-am-Main, Germany
0.005 ppm
0.2 ppb
0.01 ppm
0.01 ppm
0.01 ppm
8.7 ppb
^1 ppb
Neligan e£ al., 1965
Hoshika, 1977
Altshuller and Bellar, 1963
Lonnemann et al., 1968
Neligan e± al., 1965
Grob and Grob, 1971
Bergert ££ al., 1974
See Table 23 for details of the five locations.
-------
No data has been encountered for either a-methylstyrene or divinylbenzene in
the atmosphere.
2. Water
Tables 25 and 26 summarize data collected by the Environmental
Protection Agency in 1976 and published in December of that year on styrene
and ethylbenzene monitored in water (Shackelford and Keith, 1976). The tables
show that styrene has been most frequently noted in industrial effluents,
ethylbenzene in potable water. Also, there are more observations of ethyl-
benzene than styrene, which is the same situation for the atmospheric monitor-
ing reported in the previous section. To account for this one would have to
consider the reactivity and solubility differences of the two compounds as
well as the possibility of differences in the number and types of potential
sources (see Section II-C).
Keith (1972) monitored the contents of seven different industrial
aqueous effluents, identifying a total of 33 different compounds in them.
Styrene was found in the effluent of a petrochemical plant in which it was
neither a raw material nor a product. Styrene was also found in the effluent
of a synthetic rubber plant in which it was used as a raw material. Quantita-
tive data was not given. The analytical technique used (gas chromatography/
mass spectrometry) is easily capable of sub ppm sensitivity (see Section II-D).
Most of the water monitoring where concentrations were reported
involved potable water. One of the most detailed cases of styrene contamina-
tion of potable water was documented by Grossman (1970). Sometime between
1959-1961, two drums of styrene had been buried beneath one to four feet of
landfill at Gales Ferry, Connecticut at the conclusion of construction of a
one-family housing project. In 1962 six water wells in the area began
108
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Table 25 . Styrene Identified in Water (Shackelford and Keith, 1976)
(Monitoring dates, where available, are indicated in
parentheses)
1. Effluent from a latex plant (3/74), Louisville, Kentucky
2. Effluent from a chemical plant (3/74), Louisville, Kentucky
3. Effluent from a latex plant (10/75), Calvert City, Kentucky
4. Effluent from a chemical plant (8/75), Calvert City, Kentucky
5. River water (10/75), Water Research Center, Stevenage, Hertfordshire SGI,
England
6. Effluent from a chemical plant (8/74), Colliersville, Tennessee
7. Finished drinking water (1970), Mississippi River, Louisiana, EPA Report,
Region VI, Dallas, Texas, April, 1972
8. Effluent from a chemical plant (1970), Mississippi River, Louisiana, ibid.
9. Effluent from a textile plant (1970), Mississippi River, Louisiana, ibid.
10. Effluent from a chemical plant (8/73), Webb, Garrison, Keith, and McGuire,
EPA, Athens, Georgia
11. Finished drinking water (1/76), Bob Tardiff, EPA, Cincinnati, Ohio
12. Finished drinking water, Indiana, "Identification and Analysis of
Organic Pollutants in Water," L.H. Keith, ed., Ann Arbor Science
Publishers, June, 1976
13. Effluent from a textile plant (2/75), M. Gordon, personal communication,
Murray State University, Murray, Kentucky
14. Effluent from a chemical plant (8/74), Memphis, Tennessee
15. Finished drinking water (8/75), Grand Forks, North Dakota, "Preliminary
Assessment of Suspected Carcinogens in Drinking Water," EPA Report
to Congress, December, 1975
16. Finished drinking water, New York, ibid.
17. River water (7/75), G.A. Turk and A.E. Stanley, Ames Lab, ERDA, Iowa
State University, Ames, Iowa
18. Finished drinking water (7/75), ibid.
19. Effluent from a chemical plant, World Health Organization
109
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Table 26. Ethylbenzene Identified in Water (Shackelford and Keith, 1976)
(Monitoring dates, where available, are indicated in parentheses)
1. Finished drinking water (6/71), Anal. Chem., 44, 139 (Burnham ££ al^., 1972)
2. Finished drinking water (10/75), Water Research Center, Stevenage,
Hertfordshire SGI, England
3. River water (10/75), ibid.
4. Well water (10/75), ibid.
5. River water (11/73), Chromatog.. 7., 118 (1974)
6. Effluent from a chemical plant (8/74), Colliersville, Tennessee
7. Finished drinking water (1970), Mississippi River, Louisiana, EPA Report,
Region VI, Dallas, Texas, April, 1972
8. Effluent from a chemical plant (1970), ibid.
9. Effluent from a sewage treatment plant (2/76), Contract 68-01-3234,
Progress Report #2, University of Illinois, Champaign, Illinois
10. Effluent from raw sewage (2/76), ibid.
11. Raw water (2/76), ibid.
12. Effluent from a sewage treatment plant (8/72), A.W. Garrison, personal
communication, EPA, Athens, Georgia
13. Finished drinking water (1/76), Bob Tardiff, EPA, Cincinnati, Ohio
14. Finished drinking water (5/73), J. Chromatog., 84^, 255 (1973) (Grob, 1973)
15. River water (5/75), ibid., 112, 701 (1975) (Bertsch e£ a^., 1975)
16. River water, ibid., 715
17. Effluent from a sewage treatment plant, "Identification and Analysis of
Pollutants in Water," L.H. Keith, ed., Ann Arbor Science Publishers,
June, 1976
18. Finished drinking water (2/75), Philadelphia, Pennsylvania, ibid.
19. River water, Switzerland, ibid.
20. Effluent from a textile plant (2/75), M. Gordon, personal communication,
Murray State University, Murray, Kentucky
21. Effluent from a chemical plant (8.74), Memphis, Tennessee
22. Finished drinking water, New Orleans, Louisiana
23. Finished drinking water (8/75), "Preliminary Assessment of Suspected
Carcinogens in Drinking Water," EPA Report to Congress, December, 1975
24. Finished drinking water (8/75), Grand Forks, North Dakota, ibid.
25. Finished drinking water, New York, ibid.
26. River water (7/75), G.A. Junk and S.E. Stanley, Ames Lab, ERDA, Iowa State
University, Ames, Iowa
27. Well water (7/75), ibid.
28. Finished drinking water, Zurich, Switzerland
110
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delivering water with an obnoxious odor. The odor was due to the presence of
0.1 to 0.2 mg/£ styrene. In 1961-62 all known contaminating material was
removed from the ground and activated charcoal filters installed on the wells.
The styrene concentration (sampled ahead of the filters) began to decline and
was undetectable after 1964. Data collected over the period showed that
styrene may persist for at least two years after the removal of the contami-
nating sources under the geological conditions of the area. Despite the fact
that styrene is only slightly soluble in water, it can be easily transported
via water systems from one bedrock unit or subunit to another.
In another case of contaminated well water (Burnham et al.,
1972), 15 ppb ethylbenzene was monitored in a well in Ames, Iowa. An objec-
tionable taste and odor in the well water led to the testing which confirmed
the presence of a variety of organics, believed to be tar residues from a coal
gas plant operated in the city of Ames in the 1920"s. The tar residues were
buried in a pit hydrologically connected to the aquifer supplying the city's
water.
Styrene has been monitored in river water in the Lower Tennessee
River (Gordon and Goodley, 1971). Ethylbenzene has been monitored in the
Black Warrior River (Tuscaloosa, Alabama) (Bertsch et ad., 1975). Concentra-
tion data were not provided in either case.
Ethylbenzene has been monitored in the tap water of at least
two major cities. Grob (1973) reported ethylbenzene in the tap water of
Zurich, Switzerland as well as in the lake which is the source of Zurich's
water supply. Dowty et al. (1975) found ethylbenzene, among 60 to 70 other
organics, in commercial deionized charcoal-filtered water whose source was the
water of New Orleans, Louisiana. Such commercial deionized filtered water is
111
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used for, among other things, the preparation of carbonated beverages. Spe-
cific quantitative data were not given.
The water monitoring discussed above is summarized in Table 27.
3. Food and Other Ingested Materials
Styrene has been monitored in food products and also in several
other non-nutritive materials which humans may ingest. Polystyrene food
packaging is a potential source of styrene monomer which may migrate into the
food contained in the package. Container manufacturers have an impetus to
keep monomer levels extremely low, not only because of the potential hazards
involved in the ingestion of the monomer, but also because styrene imparts
very undesirable odors to food at relatively low concentrations. For example,
styrene can be detected in milk at 0.5 ppm and imparts a disagreeable odor
and flavor to yogurt at 0.2 ppm (Jensen, 1972). Finley and White (1967) moni-
tored styrene in milk stored in polystyrene containers for up to eight days
(presumably under refrigeration, although storage conditions were not
specified). They were unable to detect styrene in the milk. The lower limit
of sensitivity of their analytical method was 0.05 ppm. By current standards
this is not especially sensitive. It was not indicated how much, if any,
residual styrene monomer was actually present in the plastic containers which
were used in the experiment.
Kinlin et al. (1972) found both styrene and ethylbenzene in
roasted filbert nuts, along with 227 other organic compounds. Neither had
been previously reported in roasted filberts. No quantitative data were given.
The nut samples were not unusual in any way. The aim of the analyses was to
identify molecules contributing to the characteristic filbert flavor rather
than to seek contaminants.
112
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Table 27. Styrene and Ethylbenzene Monitored in Water
Compound
Location
Medium Monitored
Concentration Reference
Styrene
Styrene
Styrene
Styrene
Ethylbenzene
Ethylbenzene
Ethylbenzene
Ethylbenzene
petrochemical plant effluent no data
synthetic rubber plant effluent no data
southeastern Connecticut well water 'v-l ppra
Lower Tennessee River river water no data
Ames, Iowa well water no data
Tuscaloosa, Alabama river water no data
Zurich, Switzerland tap water no data
New Orleans, Louisiana commercial deionized no data
charcoal-filtered water
Keith, 1972
Keith, 1972
Grossman, 1970
Gordon and Goodley, 1971
Burnham ^t_ al. , 1972
Bertsch et al., 1975
Grob, 1973
Dowty e^ al., 1975
-------
Styrene has been found in four of seven samples of whiskey
screened for organics (Kahn e_t al., 1968). Two Bourbon samples (3 and 4 years
old) and one Canadian (unaged) sample of the seven did not contain styrene,
whereas one other Bourbon and two other Canadian whiskey samples (all unaged)
and the condensate from a conventional beer still all contained styrene.
Quantitative data were not given.
Styrene is a component of cigarettes and cigarette smoke.
Baggett et al. (1974) found 18 ug of styrene per cigarette in a domestic
filter blend. In addition, styrene was identified in the smoke. Styrene was
also found in the air of an unventilated smoking chamber after a machine had
smoked 30 American blend cigarettes (Jermini e£ al., 1976). The concentration
of the styrene was approximately 0.026 ppm.
Withey and Collins (1978) have recently conducted a detailed
study of styrene in polystyrene packaging and food in contact with packaging.
Levels of styrene monomer in polystyrene food containers varied from 30 to 210
ppm (limit of detection was 1 ppm). The concentrations in a variety of dairy
products ranged from 20-80 ppb in yogurt (limit of detection was 0.91 ppb) to
140-240 ppb in sour-cream (limit of detection was 13.4 ppb). The concentration
in food containers is well within FDA standards (10,000 ppm).
4. Industrial Products
Styrene and ethylbenzene have been reported in certain indus-
trial products in which their presence, if not surprising, might not neces-
sarily be expected. Styrene, for example, was found in brake lining pyrolysis
products (Fisher and Neerman, 1966), which suggests that the wearing of brake
linings may be a minor source of styrene in the atmosphere. Esposito (1968)
found ethylbenzene in a variety of industrial aromatic solvents and synthetic
114
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mixtures, many of whose formulas are proprietary. Stavinoha and Newman (1972)
found ethylbenzene in regular and premium grade gasolines. Gasoline has been
suggested (Grob and Grob, 1971) as a possible source for ethylbenzene in the
atmosphere (see Section II-C).
5. Miscellaneous Monitoring
Reichel et_ <*!_• (1977), analyzing estuarine bird samples collected
in 1970 and 1973 from the Lake St. Clair, Michigan area, found polychlorinated
styrenes in carcass and egg tissues of the Great Blue Heron (Ardea herodias).
Octochlorostyrene was detected at 0.4 ppm in two of three samples of carcass.
An average of 0.1 ppm was found in three of four samples of egg. Heptachloro
and hexachlorostyrenes were tentatively identified in the tissues as well.
The source of polychlorinated styrenes in these environmental samples is not
known. Since these are not commercially important chemicals, they may have
been formed in the environment by some as yet unknown mechanism from unknown
precursors.
115
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III. Health and Environmental Effects
A. Environmental Fate and Transport
1. Biodegradation
Both ethylbenzene and styrene appear to be susceptible to
metabolism with mixed cultures of microorganisms. Ludzack and Ettinger (1963)
examined the degradation of ethylbenzene (19 to 25 mg/£,) in Ohio River water
using 5 gallon carboys over a period of 35 days. They measured the carbon
dioxide (unlabelled) evolution compared to a control and reported their results
as percent of theoretical. Ethylbenzene did not reach more than 50% of theo-
retical over 35 days, but part of the carbon was suspected to have been lost by
volatilization. Similar results were found by Pahren and Bloodgood (1961) for
styrene and a variety of vinyl compounds. McKinney et al. (1956) showed that
phenol activated sludge was able to remove 27% of the theoretical oxidation of
500 ppm of ethylbenzene in 12 hours of aeration.
Price and coworkers (1974) conducted 20 day BOD tests on styrene
at 3, 7, and 10 mg/Jl . Their results were corrected for nitrification and
reported as percent of theoretical BOD. In 20 days, styrene had reached 85% of
theoretical while benzene was 20% and phenol was 95%.
Several studies have attempted to determine the pathways of
microbial metabolism of ethylbenzene and a-methylstyrene using pure cultures.
These studies are summarized in Table 28. In general, it appears that oxida-
tion can occur on the ring (cis-dihydroxylation) and on the side chain. When
the alkane or alkene is a straight chain, attack on the chain is favored; when
it is branched (a-methylstyrene), cis-dihydroxylation on the ring appears to be
favored.
116
-------
Table 28. Pure Culture Metabolism of Ethylbenzene and a-Methylstyrene
Reference
Microorganism
Results
Davis and Raymond, 196] Nocardia sp.
Gibson and Yeh, 1973
Gibson et al., 1973
Omori et al., 1974
Pseudomonas putida 39/D
Pseudomonas putadia
bacteria (unknown)
isolated from soil
by enrichment on
isopropylbenzene
OH
CH^CH - used as growth substrate
OH OH
'CH,
CH=CHCH
0
A
-------
Recently, Grbid and Munjko (1977) examined the ability of
streptomycetes isolated from soil and river water to utilize styrene and
a-methylstyrene as a sole carbon source. None of the soil strains were able to
grow, but four (80%) of the river water strains could grow on the chemicals.
Guillet e£ al. (1974) studied the biodegradability of a photo-
degraded polystyrene-vinyl ketone copolymer. Their result indicated that
14
after photolysis small amounts (<0.20%) of CO- are evolved from both a soil
and activated sludge environment. However, these results provide little in-
sight into the biodegradability of the styrene monomer.
2. Chemical Degradation
The available information on environmental chemical reactions
has already been reviewed in Section I-B. In general, the styrene compounds
are very susceptible to oxidation processes and under smog conditions react
very rapidly. Ethylbenzene is less reactive under smog conditions but is one
of the more reactive hydrocarbons studied. None of the compounds is expected
to hydrolyze in the environment.
3. Environmental Transport
The physical properties (Table 2) of the styrenes and ethyl-
benzene suggest that they are relatively volatile and are soluble in water at
trace quantities. Both ethylbenzene and styrene have been detected in ambient
water and air samples. The high vapor pressure of styrene (4.53 torr at 20°C)
and ethylbenzene (38.60 torr at 20°C) suggests that these compounds will exist
in the vapor state in the atmosphere and, depending upon how fast they degrade,
could be carried long distances.
These compounds in water are not likely to bioconcentrate in
biological organisms because of their relatively high water solubilities.
118
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Using the water solubilities of ethylbenzene (200,000 ppb) and styrene
(290,000 ppb) and the equation of Metcalf and Lu (1973), the biomagnification
factor is 16 and 12, respectively.
The evaporation half-life of the compounds from water can be
calculated from the molecular weight, water solubility, and vapor pressure
(Billing, 1977). The half-lives for styrene and ethylbenzene assuming a water
depth of one meter are 23.8 hours and 7.5 hours, respectively.
Some information is available which suggests that these compounds
do leach through soil. In research oriented at stabilizing soil columns with
resins in order to optically observe the soil, Wells (1963) found that liquid
styrene monomer moved readily through the column.
Grossman (1970) documented an incident where at least two left-
over drums of waste styrene that were buried 1 to 10 feet deep allowed the
migration of the chemical into bedrock aquifers that were being used for
drinking water. The styrene moved downward with water through the glacial till
and into the aquifer. The contamination persisted at least 2 years after
removal of the buried sources. Styrene migrated at least "300 feet along
joints into cones of depression resulting from small-scale pumping for indivi-
dual family dwellings." The styrene had been used to burn brush in clearing
land for the development.
B. Biological Effects
1. Toxicity and Clinical Studies in Man
a. Occupational Studies
(1) Biological Monitoring
A primary concern in evaluating the effects of styrene on
man is to first define the intensity of exposure. Biological monitoring of
119
-------
workers exposed to styrene has, for the most part, consisted of determining the
levels of styrene metabolites in urine. However, analysis of styrene in the
breath, fat, and blood has also been employed in quantitating the extent of
exposure.
Determination of the styrene metabolites, phenylglyoxylic,
raandelic, and hippuric acids in urine has been most extensively evaluated as an
index of exposure. Nevertheless, total agreement has not been reached with
regard to the metabolite which best correlates with exposure intensity or
duration. Ohtsuji and Ikeda (1970) observed that at styrene concentrations up
to 30 ppm, mandelic and phenylglyoxylic acids were both significantly elevated
in the urine (Table 29). Levels of phenylglyoxylic acid were the most sensi-
tive indicator when styrene concentrations were in the range of 1 to 20 ppm.
On the other hand, urinary hippuric acid levels did not correlate with inten-
sity of exposure at the concentrations of styrene vapor studied in this experi-
ment. However, in a more recent investigation, Ikeda et al. (1974) noted that
a significant increase in urinary hippuric acid levels was observed among
workers exposed to styrene at concentrations of 50 to 200 ppm for 160 minutes.
In this study, mandelic and phenylglyoxylic acid levels were maximally elevated
two to five hours after termination of exposure (returning to normal after about
30 hours), whereas hippuric acid levels reached a peak several hours later
(returning to normal after one to two days). The delayed appearance of hippuric
acid is consistent with the observation that it is derived from mandelic acid.
When styrene exposure was reduced to 4 to 60 ppm for 120 minutes, hippuric acid
levels were not elevated in the urine, although urinary concentrations of mandelic
and phenylglyoxylic acids were both enhanced. A comparison of the urinary
120
-------
Table 29. Metabolite Levels in Urine of Workers Exposed to Styrene"
No. of
workers
6
4
4
7
9
Styrene
concentrations
(ppm)
10-30
7-20
1-20
<1
0
Metabolites
Hippuric acid
438
(326-588)
556
(263-1175)
494
(238-1022)
309
(198-482)
350
(199-616)
in urine (ing/liter.)
Phenylglyoxlic
acid
381
(298-487)
287
(183-449)
201
(153-263)
98
(46-213)
19
(11-34)
Mandelic
acid
875
(505-1515)
473
(319-702)
310
(189-518)
137
(49-385)
92
(47-178)
Ratio
mandelic acid
Ph-glyoxylic acid
2-3
1-7
1-5
1-4
Modified from Ohtsuji and Ikeda (1970)
-------
half-lives of raandelic and phenylglyoxylic acids among male workers revealed
values of 7,8 and 8.5 hours, respectively. Philippe and coworkers (1971)
agreed that mandelic acid is more rapidly excreted than phenylglyoxylic acid,
but noted that its biological half-life increases with styrene exposure in-
tensity above 100 ppm. Thus, the measurement of urinary phenylglyoxylic acid
and the determination of the mandelic acid/phenylglyoxylic acid ratio was
suggested as a useful procedure for monitoring the degree of styrene exposure.
Quantitative correlates of styrene exposure with levels of
urinary metabolites have been attempted by others in recent years. For this
purpose, urinary levels of mandelic acid, expressed as mg/£ of urine or mg/g of
creatinine, are correlated with air concentrations of styrene. It was reported
(Harkonen j^t al., 1974) that urine samples taken at the end of an eight hour
work shift contained 3000 mg mandelic acid per liter of urine when workers were
exposed to a time-weighted average styrene exposure of 100 ppm. However,
Gotell and coworkers (1972) determined that 1000 mg/2. of mandelic acid in urine
corresponded to a time-weighted average styrene exposure of 50 ppm, and
2000 mg/£ corresponded to an exposure of 100 ppm of styrene. Moreover, these
investigators found that in a group of workers exposed to concentrations of
styrene greater than 150 ppm, a strongly negative correlation was obtained
between styrene exposure and urinary levels of mandelic and phenylglyoxylic
acids.
More recently, these surprising results were clarified by
Engstrom and coworkers (1976) who found that the half-time of elimination of
mandelic acid decreased as exposure levels of styrene increased from 23 to
248 ppm. In addition, a biphasic elimination rate was observed for mandelic
122
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acid, showing a rapid phase from 0 Co 18 hours post-exposure and a slow phase
from 19 to 64 hours post-exposure. Since dose-dependent elimination of xeno-
biotics is a commonly observed phenomenon, it may reasonably be speculated that
enhanced detoxification mechanisms (i.e., enzyme induction) may result from
high-level styrene exposures (see Section III-B-7). As a biological monitoring
tool, levels of mandelic acid in urine taken at the end of a work shift cor-
related highly (r = 0.93) with the eight-hour time-weighted average concentra-
tion of styrene in ambient air.
It is not presently possible to resolve the apparent
inconsistencies reported in mandelic acid excretion rates at levels of styrene
greater than 150 ppm. Whereas Engstrom and coworkers (1976) reported that the
excretion rate of mandelic acid increases with styrene dose, Philippe et al.
(1971) and Gotell et^ a^. (1972) found that the rate decreases. Consequently,
any program of biological monitoring for exposure to styrene will probably
require the concommitant analysis of styrene levels in air in order to ade-
quately define the potential exposure.
Analytical methods for the detection of mandelic and
phenylglyoxylic acids in urine are well-validated. Major reliance is placed on
gas chromatographic determination of the derivatized metabolites subsequent to
their extraction from urine (Buchet e_t_ al_., 1974; Bauer and Guillemin, 1976;
Lhoest et. a_l-> 1976; Engstrom and Rantanen, 1974). The inclusion of a prelim-
inary paper chromatographic separation of urine prior to gas chromatographic
analysis was reported to increase the sensitivity of the mandelic acid assay by
a factor of ten (Slob, 1973). Additional methods of analysis include colori-
metric techniques (Ohtsuji and Ikeda, 1970) and a new isotachophoretic proce-
dure which also identifies hippuric acid (Sollenberg and Baldesten, 1977).
123
-------
In an attempt to define the body burden of styrene and
ethylbenzene among 25 polymerization workers, Wolff and coworkers (1977) ana-
lyzed subcutaneous fat samples taken at various times after exposure. All 15
styrene workers who had been removed from work for less than three days had
detectable levels of styrene in the fat. On the other hand, removal from expo-
sure for more than three days was associated with an absence of styrene in the
subcutaneous fat. These analyses also revealed the presence of ethylbenzene in
21 of the 25 workers, thereby indicating a greater persistence in the body,
possibly due to its less efficient metabolism. Thus, it was concluded that
although styrene rapidly disappears from the urine and breath, indirect exposure
may still occur for several days to styrene which has been sequestered in body
fat stores. This principle is applicable to ethylbenzene as well, since it
apparently persists in the fat for even longer periods.
In a later study this same group (Wolff et al., 1978) moni-
tored urinary levels of mandelic and phenylglyoxylic acids, and blood levels of
styrene in 491 styrene polymerization workers. Styrene levels in subcutaneous
fat samples were determined in 25 workers. The limit of detection for styrene
in fat was .2 ppm., while for urinary metabolites it was approximately 10 mg/1.
Blood levels of styrene were determined below 1 ppb. Workers were divided into
groups exposed to higher than 5 ppm. styrene levels (peak levels of 8-30 ppm),
1-5 ppm. levels, and less than 1 ppm. styrene levels. In a group examined
within four hours of last exposure, the highest frequency of elevated urinary
metabolites and blood styrene concentration was found in those workers exposed
to more than 5 ppm levels (40-60%). Workers who had elevated test values showed
a correlation between urinary metabolites, blood styrene concentration, and
styrene in fat. However, in the overall population studies, urinary metabolites
124
-------
were undetectable in the majority of workers (341/477) and the correlation
between blood and urinary determinations was poor. The authors suggest that
this may be due to the different elimination kinetics of styrene in blood,
and of urinary mandelic and phenylglyoxylic acids, respectively. These
studies confirm that urinary and blood levels decrease rapidly as time from
last exposure lengthens, and that styrene levels in fat are the most prolonged
values that were measured.
Uptake and retention of styrene was determined in three
workers employed in a Swedish polymerization plant (Engstrom et al., 1978). The
concentration of styrene in ambient air was monitored continuously during the
work week in all breathing zones. Total uptake was estimated based on time
weighted inspiratory air concentrations, and adipose concentrations were deter-
mined from subcutaneous fat samples. Measurements indicated that the time
weighted inspiratory air level of styrene was 7.5-20 ppm. The mean daily styrene
uptake varied from 193-558 mg. Variations in styrene levels measured in adipose
tissue were observed during the work week. Monday morning adipose levels of
2.8-8.1 mg/kg were recorded, while Friday afternoon measurements were 4.7-11.6
mg/kg. The authors indicate that in all three workers a moderate increase (3-
7%) in adipose styrene content was seen during the work week. Longer duration
studies are needed to determine whether a cumulative effect is seen in the
adipose tissue of workers constantly exposed to styrene.
Engstrom and coworkers (1978) monitored ambient air styrene
levels in a reinforced plastics factory during a work day and determined urinary
mandelic acid and hippuric acid content in 47 workers (9 females and 38 males)
at the same facility. Measurements of air levels in different breathing zones
were carried out for 30 minute intervals over the entire day. Urinary metabolites
125
-------
were assayed from samples collected at the end of the workday. The individual
time weighted (8 hours) averages for different samples varied from 4 to 291 ppm,
with a peak sample value of over 700 ppm. Urinary mandelic acid concentration
correlated very well with the time weighted styrene air levels (coefficient3.93),
while hippuric acid level fluctuations over the working day were irregular.
Almost half of the workers (23/47) showed urinary mandelic acid levels that
indicated 8 hour exposure to more than 55 ppm styrene.
Techniques to monitor for the absorption of compounds
related to styrene and ethylbenzene (i.e., a-methylstyrene, divinyl benzene) are
not readily available in the published literature. However, a Russian study
(Aizvert, 1975) has indicated that the presence of atrolactic acid in the urine
may be used as a test for exposure to a-methylstyrene. The authors reported
that 26.2% of an inhaled dose of o-methylstyrene was excreted as urinary atro-
lactic acid during the five days following exposure.
(2) Effects on Worker Health
Numerous adverse effects on health have been attributed to
styrene exposure. In many cases, however, it is difficult to attribute spe-
cific clinical findings to styrene exposure alone. Moreover, it is not usually
possible to define the extent of exposure which corresponds to particular toxic
symptoms.
Reports from East-European countries and Russia have linked
chronic occupational exposure to styrene with: menstrual disorders and toxemia
of pregnancy (Zlobina e_t al., 1975); decreased blood glucose and increased
glucose tolerance (Chmielewski et^ al^., 1973); leukocytosis, erythrocytopenia,
muscle-chronaxia changes, decreased coproporphyrin excretion, decreased blood
126
-------
cholinesterase activity, and histological changes in some organs at exposure
levels of 1.2 and 11.7 ppm (Li, 1963); skin infections and neurasthenic syn-
drome at average exposures of 164 ppm or less for 1.8 years (Simko et al.,
1966); headache, weariness, somnolence, and dyspeptic disorders at exposures of
47 to 94 ppm (Huzl et al., 1967); and increased urinary coproporphyrin excre-
tion and elevated lactic acid dehydrogenase activity with exposures of 24 ppm
(Klein and Zak, 1969). Further reports abstracted from the foreign literature
have associated combined styrene-butadiene-ethylbenzene exposures with diseases
of the nervous system and digestive organs (Abdullaeva, 1973); decreased periph-
eral vascular tonus and stability (Alekperov e± al., 1970a; Vinokurova, 1970a);
altered myocardial function (Alekperov et^ al_., 1970b; Vinokurova, 1970b);
alterations in blood content of cholesterol, lecithin, and lipoproteins at
styrene exposure levels of 0.5 to 32 ppm (Lukoshkina, 1970; Lukoshkina and
Alekperov, 1973); and alterations in gastric juice components and gastric
mucosa function (Bashirov, 1975). Additional evidence concerning occupational
exposure to a-methylsytrene (with or without exposure to butadiene) suggested
neurological and reflex effects (Minaev, 1969; Ogleznev, 1963), liver dysfunc-
tion (Sergeta j£ al., 1975), cardiovascular disorders (Konstantinovskaya,
1972), and vitamin B... deficiency (Brawe, 1974).
Neurological symptoms in workers exposed to styrene in the
plastics industry have been studied by Klimkova-Dentschova (1962) and Roth and
Klimkova-Deutschova (1963). A group of 30 women and five men reporting to
the clinic with varied symptoms of headache, fatigue, tremors, and neurasthemic
symptoms were given neurological examinations. Average exposure time of the
group was 1.9 years at levels from 20 ppm to 130 ppm styrene. EEC abnormalities
were noted in 13/18 (72%) workers studied; these involved irregular alpha rhythms,
127
-------
alternating rapid activity and low amplitude patterns, and the presence of
theta waves. Patterns indicating sleep or reduced vigilance were also noted.
A high incidence (74-95%) of vegetative (autonomic) nervous system symptoms,
peripheral, and extra-pyramidal neurological symptoms in these styrene workers
was also reported. Exposure to other chemicals cannot be evaluated, and these
studies deal with a selected population that has already shown subjective
symptoms of toxicity.
Many years of industrial experience with styrene have
established that symptoms of mucosal irritation and general discomfort are
common complaints among exposed workers (Zielhuis e£ al., 1964). A summary of
data regarding subjective symptoms resulting from chronic styrene exposure
(average exposure below 100 ppm) is presented in Table 30. These data were
thought to support the safety of a 100 ppm exposure limit with regard to
serious or permanent health impairment (AGGIH, 1977).
On the other hand, examinations of biochemical functions
among styrene workers have indicated certain metabolic disorders. Workers with
exposure to styrene for an average period of ten years were found to have
reduced blood platelet numbers with increased platelet adhesion, which was
possibly related to disorders in lipid metabolism and thrombopoiesis (Chmielewski
and Renke, 1976). In addition, workers with long-term styrene exposures dis-
played abnormalities in blood coagulation and fibrinolysis, which could be
explained by an effect of styrene on the liver. Since workers with short-term
(one year) styrene exposures were not affected, it was presumed that the toxic
effects observed were a consequence of chronic exposure (exposure intensity not
reported). Further studies (Chmielewski and Mac, 4976) on these same workers
128
-------
Table 30. Subjective Symptoms Among Workers Processing Reinforced Polyesters'
NJ
Symptoms Group A
n
physical fatigue
apathy
mental fatigue
epigastric oppression
gastric pain
sickness
hunger
anorexia
dizziness
headache
pressure round head
feeling groggy
hyper sensitivity
against alcohol
perspiration of the hands
general perspiration
palpitations
breathlessness
drowsiness
tearflow
irritation of eyes
sneezing and coughing
nervousness
elation
agitation
nervous tension
^Modified from Zielhuis et
1 = in 0-20% of workers;
2 = in 21-40%;
3 = in 41-60%;
4 = in 61-80%;
5 = in 81-100%
= 8
4b
4
3
1
1
2
2
4
2
4
4
1
1
2
4
1
1
5
5
5
4
2
1
2
3
a^. , 1964
Group B
n = 8
5
4
5
2
1
0
0
2
4
2
5
3
1
2
4
1
2
5
4
5
2
1
0
2
2
Group C
n = 22
2
3
2
1
1
1
2
1
0
3
2
1
2
1
2
0
1
4
3
3
2
1
0
1
3
Group D
n = 6
1
1
0
1
1
1
3
3
3
2
1
2
1
1
1
0
0
3
0
5
4
1
1
0
0
Controls
n = 5
2
0
0
0
0
0
2
0
1
2
1
0
0
1
1
1
2
0
1
0
1
1
0
1
1
-------
revealed no deficiency in liver function in either group. However, workers
with long-term styrene exposure exhibited a reduction in serum levels of alpha-
and beta-lipoproteins and cholesterol. The possibility that chronic styrene
exposure may alter patterns of steroid production by the adrenal glands or
metabolism by the liver could not be statistically confirmed (Wink, 1972).
The health effects of exposure to styrene vapor in a German
production and polymerization facility were investigated by Thiess and Friedheim
(1978). Styrene levels in workroom air were generally less than 1 ppm,
with no concentration exceeding 10 ppm. Clinical disease histories and hema-
tology and blood chemistry examinations were carried out on 177 employees having
exposure durations lasting from 1-38 years. Controls consisted of workers from
another production facility which did not produce styrene monomer or polymer.
The chemical exposure pattern of the control group was not specified. No sig-
nificant abnormalities in either laboratory findings or case histories were
observed. Urinary mandelic acid levels determined on these workers indicated
that low exposure to styrene was present at these production facilities. Mor-
tality studies of workers at this same facility indicated no increase in deaths
from tumors.
An extensive clinical study of 494 styrene workers in the
United States has confirmed many of the observations of earlier investigators
(Lorimer et al., 1977). Symptoms associated with styrene exposure include
prenarcotic symptoms (13% of the workers affected), mucous membrane irritation
(18%), wheezing or tightness in the chest (11%), recurrent tracheo-bronchial
irritation (7.6%), chronic bronchitis (18.7%), and airway obstruction defined
as FEV/FVC < 75% (35.3%). In general, workers with the highest styrene expo-
sure experienced the highest prevalence of symptoms.
130
-------
Further work (Lorimer and coworkers, 1978) has analyzed
the results of this extensive health survey covering 493 production workers
at a facility manufacturing styrene and processing polystyrene. Comparisons
were made and statistically analyzed between workers classified into either
high or low exposure categories. This distinction was made on the basis of
work history, spot testing for urinary styrene metabolites, and some limited
air sampling data obtained through NIOSH and the production company. Groups
were subdivided into three sections based on duration of exposure to styrene.
Statistically significant differences between high and low exposure groups were
noted in several categories. These included acute symptoms such as lightheadedness,
dizziness, and headache, and lower respiratory symptoms such as coughing and
wheezing. Relative lymphocytosis was seen to increase in the high exposure group
as the duration of exposure in this group increased. Large pulmonary airway
obstruction was increased in workers showing detectable urinary mandelic acid
when compared to workers in whom this urinary metabolite could not be detected.
Liver gamma-glutamyl transpeptidase levels were elevated more frequently in the
high styrene exposure group (1.7% vs. 7.2%). Lowered nerve conduction velocities
were recorded in the high exposure workers (^16% of those tested). Lymphocyte
karotyping was carried out on a small number of individuals (5 test, 2 control).
Two of the test subjects had a high number of chromosome gaps and breaks; these
two had the longest incidence of high styrene exposure (>20 yrs.) in the test
group. Interpretation of these findings is complicated by several factors. For
over one half the period covered by this study (1943-1963), this facility used
benzene in production, and thus long term employees were exposed to an agent
which produces well documented liver and hematological effects. The karotyping
results were successful in too few of the subjects tested to draw any inferences
concerning chromosome breaks.
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Among the more significant recent findings concerning
occupational exposure to styrene are reports of its effects at low levels on
mental functions. Workers were examined who had long-term exposure (mean
4.9 years) to styrene at low levels (urinary mandelic acid levels less than
674 mg/£, corresponding to an 8 hour TWA exposure of 2.5 ppm) and at higher
levels [mandelic acid levels more than 1,762 mg/£, corresponding to an 8 hour
TWA exposure of 75 ppm] (Lindstrom £t al., 1976). Although the comparison
between exposed and non-exposed workers showed few statistically significant
differences in psychological functions (visual inaccuracy and a high level of
inhibition in personality tests), comparisons between low and high exposure
groups of workers revealed greater differences. Visuomotor inaccuracy and poor
psychomotor performance were significantly related to high mandelic acid con-
centrations in the urine. Moreover, mildly abnormal electroencephalograms
(EEC1s) were found in 23 out of 96 styrene-exposed workers (24%), which cor-
responded to higher mean mandelic acid concentrations than in workers with
normal EEC's (Seppalainen and Harkonen, 1976). Symptoms of peripheral nerve
dysfunction, as measured by nerve conduction velocity, were inconsistent and
not indicative of an exposure-related trend. However, Savolainen (1977) has
recently reported that styrene and styrene oxide undergo limited binding to
central nervous system macromolecules and can elicit weak neurotoxic (encephalo-
pathy and neuropathy) effects.
Harkonen and coworkers (1978) have examined neurophysiological
and psychological effects in 98 male workers exposed to styrene in 24 reinforced
plastic facilities. Workers were placed into one of four groups based on their
urinary mandelic acid concentrations. An increase of abnormal electroencephalo-
grams (from 10% to 30%) was seen when subject groups showing <700 mg/£ mandelic
132
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acid were compared. Visuometer accuracy showed impairment at mandelic acid
levels of >800 mg/fc, and psychometer performance was affected when mandelic
acid levels exceeded 1,200 mg/fc. Intellectual performance was not found to
have changed after work in styrene facilities, as measured by standard intelli-
gence testing. The authors indicate that these effects are seen at levels of
exposure that correspond to an 8 hour time weighted average of 55 ppm or less.
Neurophysiological testing of thirty three styrene workers has
also been described by Rosen and coworkers (1978). Three groups of workers
exposed to styrene during different manufacturing or production processes were
compared to 17 patients showing neurological disorders from mixed solvent exposure
and a control group without solvent exposure. The ten styrene workers who showed
symptoms of neuropathy, similar to the symptoms observed in the mixed solvent
group, were from the group exposed to the highest levels of styrene. This was
in a polyester boat facility where 1974 measurements indicated a mean level of
125 ppm styrene. Earlier conditions at this facility indicate that higher levels
of exposure were likely. The observed neurological changes included altered
sensory nerve (median, ulmar) action potential, some decreased sensory nerve
conduction velocity, diffuse slow EEC activity, and central and fronto-central
fast EEC activity. The diffuse slow pattern incidence did not correlate with styrene
exposure intensity. The authors conclude that EEC changes were either too small
or too non-specific to aid in styrene exposure diagnosis, while sensory nerve
measurements appear to show good sensitivity to styrene effects.
Neurological studies were carried out on six volunteers (3 styrene
workers, 3 normal subjects) who were exposed to styrene vapor at 50-300 ppm for
ninety minutes (Oltramare jit al., 1974). At exposure levels of 100 ppm and
200 ppm, the three styrene workers showed decreased performance in tests of
133
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reaction times to visual stimuli and visual-acoustic stimuli (compared to
results from pre-exposure testing). Since this work was carried out on only
three subjects, further experimentation is needed to confirm the results noted.
Concern over the leukemogenic and clastogenic effects of benzene
have prompted a closer examination of structurally related compounds for their
ability to induce chromosome damage in somatic cells. Thus, it has now been
demonstrated that among workers chronically exposed to styrene an increased
incidence of chromosomal aberrations occurs in cultures of their blood lympho-
cytes (Meretoja &t^ aj.., 1977). Ten styrene-exposed workers and five unexposed
controls were used for the study. Absorption of styrene was confirmed by the
presence of mandelic acid in the urine, although an accurate estimate of total
exposure could not be made. The incidence of chromosome abnormalities (pri-
marily chromosome-type breaks) ranged from 11 to 26% in the cells of styrene-
exposed workers, as compared to three percent or less in the control group.
The possibility that these workers may also have been exposed to other chemi-
cals, either on the job or at home, could not be completely eliminated. Never-
theless, since exposure to styrene was confirmed by metabolite identification,
a causal relationship was strongly implied.
A follow up study on these same subjects was carried out one year
later (Meretoja et^ a_l., 1978). Urinary mandelic acid levels in 9/10 workers
studied were lower than those observed one year earlier. The frequency of
abnormal lymphocytes (both stable and unstable changes) in styrene workers varied
from 10-26%, while controls showed a 1-4% frequency. The authors conclude that
both the pattern and frequency of lymphocyte aberrations has remained the same
over the one year period. This incidence of aberrations is higher than that
reported for either benzene or vinyl chloride workers.
134
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Flieg and Thiess (1978) have carried out similar studies on
lymphocyte aberrations in workers exposed to styrene in different types of
manufacturing facilities. Workers in styrene manufacturing plants and polystyrene
manufacturing plants showed low urinary mandelic acid levels and no increase in
chromosome aberrations over controls. Workers exposed to styrene in a plant
processing unsaturated polyester resins had elevated urinary mandelic acid levels
and showed an increase in the frequency of aberrant lymphocytes. Both inclusive
and exclusive gaps were increased over controls. In 14 workers the range
in frequency of inclusive chromosome gaps was 4-20%, while the mean in twenty
controls was 5.5%. Ten of the fourteen workers showed a higher percentage of
inclusive gaps than the control mean. The authors comment that workers in this
last facility came in contact with various solvents during their work. The use
of peroxides in the curing process will generate styrene oxide in the working
area atmosphere and this chemical could be the agent responsible for the lymphocyte
effects seen (based on its capability to induce mutations during in vitro tests).
Hematological investigations on nine workers exposed to styrene
vapors have been carried out by Oltramare and coworkers (1974). Four workers,
involved in three different types of manufacturing operations using styrene resins,
showed lymphocytosis (38-47% lymphocytes in peripheral blood). Exposure ranges
for the different facilities were estimated at 10-35 ppm styrene, 12-82 ppm, and
10-560 ppm.
b. Epidemiologic Studies
Serious concern has recently arisen over the health hazards
of styrene as a result of reports showing an excess incidence of leukemia among
workers in the styrene-butadiene rubber industry. It was first reported in
1976 that a six-fold excess of leukemia and lymphoma was found among workers at
135
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a styrene-butadiene plant (McMichael e_t al^, 1976). Subsequent to that report,
a briefing on styrene-butadiene was called by the National Institute for
Occupational Safety and Health on April 30, 1976, to review the hazards of
styrene-butadiene production and to gather additional information (National
Institute for Occupational Safety and Health, 1977). Reports of an excess of
deaths attributable to leukemia and lymphoma at several plants in the United
States were presented. A study of nine leukemia cases found in two styrene-butadiene
rubber production plants in Fort Neches, Texas indicates that these workers had
a long duration of potential exposure (range of exployment = 17-28 years)
(Meinhardt £t al., 1978).
Mortality data on 560 styrene-polystyrene polymerization
workers at one plant has been reviewed by Nicholson and coworkers (1978). This
group, representing five years or more of work experience, did not show an
increased frequency of death from cancer. However, review of an additional
444 death certificates of employees with six months or more of work experience
at this plant showed twelve deaths resultant from leukemia or lymphoma. Since
the death certificates were randomly collected, the authors state that further
analysis should be conducted before conclusions can be drawn.
The lack of detailed information concerning simultaneous
exposure to chemicals other than styrene (e.g., benzene) and the need for more
extensive epidemiologic studies precludes a definitive judgement at this time.
In addition, it has been reported (Frentzel-Beyme e_t al., 1978) that in a study
of West German polystyrene workers there was no evidence of an excessive incidence
of leukemia. However, the lack of leukemia cases may be due to extremely low
styrene exposures (currently less than 1 ppm). Urinary mandelic acid levels in
61/67 workers tested at this facility were less than 50 mg/&.
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c. Controlled Metabolic Studies in Humans
(1) Absorption and Excretion
The uptake of various solvents, including styrene and
ethylbenzene, has been determined from studies where exposure has occurred by
inhalation or direct contact with the skin. Astrand and coworkers (1974)
performed a detailed investigation of the uptake and elimination of styrene in
human volunteers exposed to concentrations of 50 and 150 ppm styrene in air.
The absorption of styrene across the alveolar membranes and into arterial blood
was found to be extremely rapid, indicating high solubility of styrene in the
blood. Increased ventilation, as produced by light work, markedly increased
the absorption of styrene because the blood is exposed to greater amounts of
solvent-containing air. Thus, when alveolar ventilation was tripled by light
exercise, the concentration of styrene in arterial blood was tripled, whereas
the alveolar concentration of styrene increased only slightly. Therefore,
measurement of the concentration of styrene in alveolar air provides a poor
index of the extent of absorption. Ranking various solvents according to their
/
percentage of uptake based on blood and tissue solubility produced the fol-
lowing results (largest uptake first): styrene, aromatic components of white
spirit, toluene, trichloroethylene, aliphatic components of white spirit,
methylene chloride, and methylchloroform (Astrand, 1975).
Styrene can be detected in alveolar air up to 24 hours
after termination of exposure (30 minutes) at 50 or 150 ppm (Astrand et^ al.,
1974). Stewart and coworkers (1968) have noted that styrene excretion from the
lung is rapid and exponential, but dependent on the concentration and duration
of exposure. It was calculated that 1.2% of an absorbed dose of styrene
(117 ppm x 2 hours) was excreted via the lungs within the first four hours
137
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after exposure. By comparison, Astrand and coworkers (1974) determined that
50% of an absorbed dose (50 ppm x 30 minutes) of styrene was excreted in the
urine as mandelic acid. Others (Bardodej and Bardodejova, 1970) reported that
64% and 857, of the absorbed doses of inhaled ethylbenzene and styrene, respec-
tively, were excreted as urinary mandelic acid (Table 31). These investigators,
however, were unable to detect large amounts of unchanged styrene or ethyl-
benzene in expired air following eight hours of inhalation exposure. It was
suggested (Astrand et al., 1974) that failure to correct for background levels
of mandelic acid excretion and the low concentrations employed (22 ppm styrene)
may account for the discrepancies.
Pulmonary absorption and excretion of styrene was determined
in six volunteers by Fernancez and Caperos (1977). Styrene exposure varied from
70-200 ppm for periods of 4-8 hours. Pulmonary absorption studies indicated a
retention of 81.8-92.7% of styrene administered at various concentrations.
Alveolar pulmonary concentrations of styrene declined rapidly within one hour
after the termination of exposure at all levels. The proportion of styrene eliminated
by the lungs was only 2.6% of the total absorbed dose. Since blood levels of
styrene decline rapidly following exposure, metabolism and urinary excretion
play the major role in elimination.
Fiserova-Bergerova and Teisinger (1965) have conducted similar studies of
pulmonary retention of styrene vapor in seven volunteers exposed to concentrations
of 15-38 ppm levels. Exposure periods were for five hours. Styrene retention
was from 47-73% following inspiration and did 'not change during the exposure
period. Alveolar air contained about 6% of the inspired styrene. Elimination of
styrene from alveolar air showed half lives of 1.7 minutes and 7.6 minutes
thus indicating a two compartment elimination model. After the termination of
exposure styrene could not be detected in exhaled breath.
138
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Table 31. Retention, Biotransformation, and Elimination of Ethylbenzene and
Styrene and Their Metabolites in Man
Concentration of vapor in the
inspired air (ppm)
Duration of inhalation (hours)
Percentage of vapor retained
in the respiratory tract
Ethylbenzene
23; 43
46; 85
8
64
Styrene
22
8
61
Excreted in expired air in unchanged form
after inhalation was terminated
Traces
Percentage of retained dose eliminated as:
Mandelic acid
Phenylglyoxylic acid
Methylphenylcarbinol
Acetophenone
Styrene oxide
Phenylethvleneglycol
u-Hydroxyacetpphenone
Hippuric acid
Mercapturic acid
64 85
25 10
5 0
Not demonstrated0
Elevation not demonstrated
Bardodej and Bardodejova, 1970
Arithmetic averages of eighteen experiments with ethylbenzene, thirteen with
styrene
By the methods used (e.g., less than 2%).
139
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Experiments on the uptake and elimination of styrene following
inhalation exposure of seven volunteers has been reported by Engstrom and co-
workers (1978). Subjects were exposed to 50 ppm styrene at rest for 30 minutes,
given a twenty minute recovery, and then exposed for three consecutive 30 minute
periods with increasing work on a bicycle. The mean retention under conditions of
rest or work was 63% of the inspired styrene. During the last 30 minute work
period, total styrene taken up was 5-6 times greater than during the initial
rest period, indicating greater ventiliation rate effects. Elimination of
styrene by the airways during 19 hours after exposure was about 3% of the total
styrene retained. Adipose tissue samples retained measurable styrene for as
long as thirteen days following exposure. The estimated half life of styrene in
adipose tissue was from 2-4 days. The estimated percentage of styrene sequestered
in adipose tissue was 8% of the total retained styrene. However, this value will
be effected by the size of the total body fat depot. The authors state that since
adipose tissue shows a slow elimination rate the risk of styrene accumulation
in workers may be present.
Ramsey and Young (1978) studied the pharmacokinetics of inhaled
styrene in four volunteers exposed to 80 ppm for six hours. Blood levels of
styrene were shown to decline rapidly after exposure was terminated, with half
lives calculated at 16 hours and 13 hours for the two compartments of the model
constructed (blood=lst compartment, fat=2nd compartment). Based on this model
and the derived values, the authors conclude that no long term accumulation of
styrene will occur in workers exposed to 80 ppm styrene over a five day work
week. This conclusion is not in accord with those of Engstrom (1978) and reflects
several differences in the two studies. Static exposure was used in the Ramsey
study, and body fat was assumed to constitute 10% of the body weight. In the
140
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Engstrom study the derived half life of styrene in adipose tissue was considerably
longer than the value applied to the second compartment of the Ramsey model.
Correlation of urinary mandelic acid and phenylglyoxylic
acid levels with controlled styrene exposures has been reported by Guillemin
and Bauer (1978). Nine subjects were exposed to styrene vapor at 40 to 200 ppm
for four to eight hours. Rate constants for elimination of these two metabolites were
not effected by level or duration of exposure. The best correlation of metabolite
levels with styrene exposure (.91) was obtained when the sum of both metabolites
was cummulated over four days of measurements. For samples taken at a single time
point, either mandelic acid measured at the end of the work shift, or the sum
of mandelic acid and phenylglyoxylic acid measured on the morning after the last
exposure, gave relatively poor correlations (.71 or .77).
Exposure of the skin to ethylbenzene or styrene leads to
significant absorption (Dutkiewicz and Tyras, 1967; 1968). The rate of skin
absorption for ethylbenzene and styrene was considerably greater than for other
common solvents (Table 32). In addition, it was shown that the amount of
absorbed styrene or ethylbenzene excreted as urinary mandelic acid was much
less when exposure occurred by the skin as opposed to inhalation. These re-
sults indicate that the metabolic disposition of these compounds may be de-
pendent upon the route of exposure.
The percutaneous absorption of styrene vapors in ten human
volunteers has been studied by Riihimaki and Pfaffli (1978). Subjects were
exposed to 600 ppm styrene for 3 1/2 hours, during which time three ten minute
work intervals were included. Full face respirators provided inhalation protection.
Blood levels of styrene reached a plateau in three hours (during exposure), and
then declined rapidly in the next four hours after the termination of treatment. The
141
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Table 32. Skin Absorption of Styrene and Ethylbenzenec
Substance
Rate of Absorption
(mg/cm2/hr)
24 Hour Mandelic
Acid Excretion
I of absorbed dose)
Ethylbenzene
Ethylbenzene from aqueous
solutions (112-156 mg/X,)
Styrene
Styrene from aqueous
solutions (66.5-269 mg/£)
Aniline
Benzene
Nitrobenzene
Carbon Bisulfide
22-33
0.11-0.21
9-15
.040-.180
0.2-0.7
0.4
0.2-3.0
9.7
4.6
13
Data from Dutkiewicz and Tyras, 1967;1968.
142
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blood levels of styrene observed were comparable to those seen following inhal-
ation exposure to ^20 ppm styrene. The authors estimated that percutaneous
absorption of this level of vapor is ten times more effective than with the pure
liquid compound.
(2) Physiologic Effects
The dose-related physiologic effects of acute styrene
exposure in humans have been studied using controlled inhalation experiments.
When five volunteers were exposed for one to seven hours to styrene at 50, 100,
200, and 375 ppm, adverse effects were noted only at the highest concentration
(Stewart et al., 1968). Symptoms related to the exposure included mild eye
irritation within 15 minutes and impairment of neurological function (manual
dexterity; coordination) within one hour. In a similar study, Gamberale and
Hultengren (1974) found that inhalation of styrene at 350 ppm caused a signi-
ficant impairment in tests of reaction time. However, no performance decre-
ments in tests of perceptual speed or manual dexterity were noted at this
concentration. With acute exposures below 350 ppm, styrene apparently had no
effect on psychological or neuromuscular functions. Nevertheless, it should be
noted that duration of exposure, rather than intensity, may have an important
bearing on the physiologic actions produced by styrene, since arterial blood
concentration continued to increase throughout the two-hour exposure period.
Earlier studies have established that high level
styrene exposure (800 ppm for four hours) to human volunteers was associated
with impaired psychomotor responses during tapping rate and steadiness tests
(Carpenter ej: al., 1944). In addition, styrene at the 800 ppm level produced
immediate eye and throat irritation, increased nasal mucus secretion, and
subjective symptoms of drowsiness, weakness, unsteadiness, and lingering
metallic taste.
143
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Controlled human studies involving exposure to ethyl-
benzene or a-methylstyrene which detail the physiologic effects of exposure
have not been encountered.
d. Poisoning Incidents
Reported cases of accidental styrene poisoning are rela-
tively rare. However, from the limited data which are available, a possible
relationship is suggested between acute styrene intoxication and transient
visual impairment.
It was first reported in 1964 that a man working in the
fiberglass industry and having repeated exposure to styrene developed a sudden
and painless deterioration of vision (Pratt-Johnson, 1964). A general medical
and neurological examination revealed no abnormalities other than a presumed
bilateral toxic retrobulbar neuritis caused by styrene exposure. The patient's
vision slowly returned to normal (20/20) after seven months, with complete
recovery of visual acuity and visual fields within a year. In a more recent
report of accidental styrene poisoning, Schwarzmann and Kutscha (1971) de-
scribed the case of a student who developed blind spots in the centers of his
eyes within a half-hour of spilling styrene on his left hand. Vision improved
within one and one-half hours of the exposure, although the patient continued
to suffer from an intense headache, numbness, hot and cold spells, and shaki-
ness. Recovery was apparently complete within twelve hours after the initial
exposure.
Published reports have not been encountered which describe
incidents of poisoning by ethylbenzene, a-methylstyrene, or divinylbenzene.
144
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2. Effects on Non-Human Mammals
a. Absorption/Excretion Studies
Early experiments demonstrated that styrene is rapidly
distributed in mammalian tissues and quickly eliminated from the body (Danishefsky
and Willhite, 1954). Although the results were limited by the availability of
14
sensitive analytical techniques, it was nevertheless shown that (B- C-styrene
is widely and maximally distributed to all major tissues within one hour of
subcutaneous injection in the rat. Within 24 hours, 85% of the administered
radioactivity was excreted; principally via the urine (71%) but also in the
feces (<3%) and as respired C0_ (12%). Almost three percent of the administered
dose was recovered within 24 hours as unchanged styrene exhaled from the lungs.
More recent studies (Sauerhoff e_£ al_., 1976; Sauerhoff and
Braun, 1976) confirm, for the most part, the observations of earlier investi-
gators regarding styrene disposition. The oral administration of ring-labelled
14
C-styrene to rats of both sexes at doses of 50 and 500 mg/kg resulted in
excretion of more than 90% of the radioactivity in urine after 72 hours
(Table 33). Elimination of radioactivity from body tissues was complete within
72 hours.
The kinetics of urinary metabolite elimination in rats
following lip administration of 900 mg/kg styrene has been reported by Ogata
and Sugihara (1978). Urine samples were separated using liquid chromatography
and analyzed for mandelic acid, phenylglyoxylic acid, and hippuric acid content.
The levels of all three metabolites peaked at 24 hours and then progressively
declined.
A greater percentage of styrene excreted unchanged from the
lungs of rats treated at 500 mg/kg was indicative of saturation of metabolic
145
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14
Table 33. Percent of Administered C Activity Recovered in
72 Hours Following a Single Oral Dose of 50 or
500 mg/kg 14C-Styrened
Urine
Feces
Expired Air
50 mg/kga
94.6 + 1.9
3.7 + 1.3
1.3 + 0.5
500 mg/kga
90.3 + 6.4
1.5 + 0.6
8.9 + 4.4
Tissues and Carcass
Cage Wash 0.4 + 0.1 0.9 + 0.4
Recovery 100.2 +1.3 98.7+6.1
Values are mean + S. D. of 2 male and 2 female rats.
b 14
Values for C activity in expired air represent expired styrene.
c 14
No detectable C activity found in tissues or carcass.
dSauerhoff et al., 1976.
146
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pathways for styrene biotransformation (Sauerhoff e£ al., 1976). Moreover,
urinary excretion of styrene at 50 mg/kg was biphasic (half-life values of
1.29 + 0.19 and 8.13 + 1.22 hours), whereas at 500 mg/kg excretion was mono-
phasic (half-life value of 6.74 + 0.67 hours). Sex differences in the excre-
tion of styrene in expired air, with males excreting about twice as much styrene
as females at both dose levels, probably resulted from the sequestering of
styrene in females due to their greater fat deposits.
Results obtained with rats following an inhalation exposure
14
to C-styrene at either 60 or 600 ppm for six hours generally confirmed the
results of oral exposure studies (Sauerhoff and Braun, 1976). In this case,
however, elimination of radioactivity in the urine was biphasic at both expo-
sure levels. Half-life values for excretion (terminal phase) were 14.9 +
14
6.5 hours and 19.2 +_ 3.7 hours at exposures of 60 and 600 ppm C-styrene,
respectively. Sauerhoff and Braun (1976) cited additional evidence which
demonstrated that a disproportionate increase in blood levels of styrene
results from increasing inhalation exposures (i.e., a twenty-five fold increase
in blood levels with a twelve-fold increase in styrene concentration). This
observation suggests a saturation of biotransformation mechanisms with in-
creasing intensity and/or duration of exposure. It was further observed that
the half-life value for styrene elimination increased from 24.5 minutes to
44.8 minutes when exposures were increased from 45 ppm (5 hours) to 520 ppm
(5 hours). Thus, it is possible that greater amounts of styrene are deposited
in body fat when excretion mechanisms are saturated.
The toxicologic significance of styrene at exposure levels
where saturation of biotransformation mechanisms occur is not clear. However,
by analogy to other aromatic toxicants (Gillette e± al., 1974), it can be shown
that a disproportionate accumulation of bioactivated toxic intermediates may
147
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occur when excretion mechanisms are overloaded. In the case of styrene, one
can speculate that an abnormal accumulation of the reactive intermediate styrene
oxide may accompany inhalation exposures in rats which exceed 600 ppm or oral
exposures of 500 mg/kg. Nonetheless, data are not available to confirm this
hypothesis.
The pharmacokinetics of styrene uptake in the rat following
intravenous and inhalation administration has been described by Withey (1978). A two
compartment model was used to evaluate the biexponential elimination curves
determined for blood and several organs (heart, brain, liver, spleen, and kidney).
These curves indicated that distribution of styrene to organs occurred rapidly
and that elimination kinetics were similar for each organ. The time to reach
blood saturation levels increased as the inhalation exposure levels of styrene
(44.8 to 2,417 ppm) increased. The apparant volume of distribution calculated
for this model (230 ml) was about ten times the blood volume and indicated exten-
sive distribution to organs outside the blood compartment. Brain, kidney, and
spleen showed higher levels of styrene than peripheral blood after varied inhal-
ation exposures to styrene (470 to 2144 ppm), and perirenal fat showed the
highest levels observed at eight to ten times the level found in other organs,
confirming the high lipid solubility of styrene. Elimination of styrene follow-
ing inhalation exposure at 2,417 ppm indicated blood half lives of 5 minutes and
320 minutes for the compound disappearance rates, while organ half life values
were approximately five minutes and 35 minutes respectively.
Accumulation of styrene in rat brain and perinephric fat
following 2-11 week exposures of rats to 300 ppm vapor was studied by Savolainen
and Pfaffli (1977). Peak levels in both tissues were observed in 4 weeks, after
which levels declined progressively with time. Perinephric fat styrene content
148
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was 40-70 times higher than brain content. The authors believe that adaption
takes place involving metabolizing enzyme induction.
Teramoto and coworkers (1978) have examined the distribution
of styrene in the tissues of rats exposed to 700 ppm styrene for four hour inter-
vals. Concentrations of styrene for the following tissues were measured:
adipose tissue, liver, brain, kidney, blood, spleen, and muscle. Levels measured
were highest for adipose tissue and lowest for muscle. All tissues showed a
similar biological half life of ^2 hours, except for adipose tissue which was
longer (levels detectable after 20 hours). Further investigations by this
group (Teramoto, 1978) indicated that multiple exposures (5x4 hours) to 700
ppm styrene produced tissue distribution and elimination of compound similar
to that observed after a single exposure. Repeated intraperitoneal administra-
l
tion of styrene (5 doses separated by 6 hr. intervals) at 350 mg produced
a trend of increasing styrene concentration in adipose tissue.
The concentration of styrene in the principal organs of
rats and mice has been studied following inhalation and dermal exposures
(Shugaev and Yaroslavl, 1969). Table 34 shows that exposure of rats to an LC
dose (11.8 mg/£) for four hours produced the greatest concentration of styrene
in the perinephric fat. Absorption of styrene through the skin (tail) of rats
also caused accumulation of significant quantities of the chemical in the brain
and liver. These values were 50 to 70 percent of the concentrations found
after inhalation exposure.
Mice exposed to lethal vapor concentrations (21.0 mg/Ji
=4930 ppm) of styrene accumulated the compound in the brain at a mean level of
18.02 milligram percent. This tissue concentration was nearly the same as in
rats similarly exposed at lethal levels (Shugaev and Yaroslavl, 1969).
149
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Table 34. Styrene Content in Rat Organs Following Inhalation and Dermal Exposures'
Route of
Administration
Duration and
Concentration
Styrene Content in Rat Organs
Brain
Liver
Kidney
Spleen Perinephric fat
Inhalation
11.8 rng/d for
four hours
25.0 20.0 14.7 19.1 132.8
(17.7-32.4) (12.7-27.3) (2.8-26.7) (11.1-27.1) (109.9-155.7)
Ul
o
Dermal undiluted styrene
(tail immersion) for one hour
14.2 14.7
(11.1-17.3) (10.7-18.7)
Data from Shugaev and Yaroslavl, 1969.
Milligram percent; mean concentration with confidence limits computed at p = 0.05.
-------
b. Metabolism and Pharmacology
The metabolic fate of styrene in laboratory mammals has
been carefully investigated by numerous researchers for more than thirty years.
It was originally reported (Spencer £t al., 1942) that in rabbits and rats
styrene is oxidized to benzoic acid, indicating cleavage at the vinyl double
bond. Later, it was shown that styrene is quickly metabolized and predomi-
nantly excreted via the urine, probably in conjugated form (Danishefsky and
Willhite, 1954; Smith et al., 1954).
The proposed metabolic pathways of styrene biotransformation
in mammals are presented in Figure 12. It should be noted that the amounts of
particular styrene metabolites produced (e.g., hippuric acid) will vary from
rodents to man (Leibman, 1975).
Among the various metabolites to be identified in the bio-
transformation of styrene in vivo were phenylethylene glycol (El Masri et: al.,
1958), hydroxyphenethylmercapturic acid (James and White, 1967), hippuric acid
(Spencer e_t al., 1942), 1- and 2-phenylethanol, vinylphenol (Bakke and Scheline,
1970), mandelic acid, and phenylglyoxylic acid (Ohtsuji and Ikeda, 1971). The
major urinary metabolites of styrene following either oral or inhalation expo-
sure in rats are mandelic, phenylglyoxylic, hippuric, and benzoic acids
(Sauerhoff ££ al/> 1976; Sauerhoff and Braun, 1976). The relative percentages
of the various metabolites formed were found to be dose- and sex-related,
however.
Further characterization of styrene metabolites formed after
14
i.p. injection of C styrene (label at the 8 position) into male rats was reported
by Pantarotto e£ al., (1978). Ethyl acetate extracts of urine treated with
trimethylanilinium hydroxide were analyzed using gas chromatography. Several
151
-------
4-Vinyl phenol
CH2
CH
Ln
OH
CH,
CH
Styrcne
Microsomes
NADPH
CH,
HC-OH
CH,
I >
CH
Styrene
Oxide
Monoglucuronide
CH2OH
CHOH
Phenylethylene
Glycol
1—Phcnylethanol
•*•
CH2OH
CH,
CH-S-CH2CH2COOH
HO-CH NHCOCH3
CH2OH
Mandelic Acid Phenylglyoxylic Acid
COOH COOH
I I
CHOH
COOH
Benzoic
Acid
CH-S-CH2-CHCOIMHCH2COOH
NHCOCH2CH2CHCOOH
I
2 - Pheny lethanol Hydroxyphenothyl
Mercaptunc Acid
c = o
CONHCH2COOH
Hippuric
Acid
NH,
S-(1 -Phenyl-2-HydroxyethyI) - Glutathione
Figure 12. Possible Pathways for Metabolism of Styrene In Mammals
-------
unknown peaks were isolated by thin layer chromatography and characterized with
mass spectrometry as containing phenolic derivatives of hippuric acid, mandelic
acid, benzoic acid, and styrene. The authors postulated the formation of short
lived styrene 3,4-epoxide and other unstable arene oxides as precursors
of these phenolic metabolites. Support for this postulated pathway comes from
14
in vitro binding studies with C-phenylethylene glycol (label unspecified),
which indicate that activated rat liver microsomes catalyzed the covalent binding
of this compound (blocked at the hydroxyl positions) to microsomal proteins. It
is difficult to assess the biological significance of this postulated metabolic
pathway, since no quantitative comparison of the amounts of phenolic metabolites
to total metabolites is presented.
Seutter-Berlage and coworkers (1978) have identified mercapturic acids in
the urine of rats administered 250 mg/kg styrene i.p. for fifteen days. Sulfur
conjugates were found at both of the side chain carbon positions indicating prior
formation of styrene oxide and glutathione attack on the ring system.
Styrene oxide was shown to be formed from styrene by rabbit
liver microsomes in vitro (Leibman and Ortiz, 1969; 1970), and by microsomes
from the liver, lung, and kidney of rats (Salmona et_ al^., 1976). However,
styrene oxide has not been detected in animal studies conducted ±n vivo.
Nevertheless, it is now believed that the microsomal metabolism of alkyl-
substituted aromatic compounds in general will produce unstable arene oxide
intermediates (Kaubisch e£ al., 1976).
Studies on the metabolism of styrene oxide in the rat and
rabbit indicated that both a glutathione conjugate and phenylethylene glycol
are formed by the enzymatic actions of glutathione S-transferase and epoxide
hydrase, respectively (Ryan and Bend, 1977; James e£ al., 1976). Therefore, it
153
-------
has been shown that styrene oxide may be an intermediate in the production of
the major metabolites of styrene j.n vivo. The toxicologic significance of styrene
oxide as an obligatory intermediate in the metabolism of styrene relates to the
reputed role of epoxide metabolites in cytotoxicity and carcinogenesis by aromatic
hydrocarbons (Sims and Grover, 1974). Thus, one can speculate that if the
enzymatic conversion of styrene oxide to soluble metabolites is impaired or
overloaded such that an accumulation of the epoxide occurs, then the potential
for malignant transformation is increased.
Indeed, Sauerhoff and coworkers (1976) indicated that at
high levels of styrene exposure to rats, alterations in metabolite ratios in
urine were obtained. These results were indicative of dose-dependent styrene
metabolism and raised the possibility that saturation of metabolism at high
exposures may lead to a build-up of styrene oxide in the body. Studies on the
specific toxic and mutagenic effects of styrene oxide underscore the reasons
for concern regarding possible health consequences (see Sections III-B-2-f and
III-B-2-g). Furthermore, recent studies have established that in the rat lung,
microsomal mono-oxygenase activity for the formation of styrene oxide exceeds
the activity of epoxide hydrase which degrades styrene oxide (Salmona et al.,
1976). Thus, it seems likely that the lung may be a sensitive target organ for
styrene toxicity. On the other hand, kinetic data for glutathione-S-transferase
in the rabbit lung indicated that a very high concentration of styrene oxide
would be required to saturate the enzyme (James ej^ al_., 1976). Therefore,
unless a disturbance leading to glutathione depletion occurred _in vivo, it is
unlikely that an excess of styrene oxide would accumulate in the lung following
exposure to styrene.
154
-------
The relationship between reduced liver gluthathione levels pro-
duced by styrene and liver toxicity was studied in hamsters by Parkki (1978).
Animals treated with 6 gm/kg intragastric styrene showed 85% depletion of liver
glutathione content following sacrifice at 24 hours. Pretreatment one hour before
and seven and 15 hours after styrene administration with 200 mg/kg methionine result-
ed in a partial protection against this depletion and reversed elevated serum
alanine aminotransferase levels induced by styrene. Administration of 500
mg/kg diethyl maleate one hour before and 15 hours after styrene increased the
observed alanine aminotransferase elevation, indicating a potentiating effect
of sulfhydryl depletion with styrene induced liver toxicity. Based on the no
effect level of styrene on liver alanine aminotransferase, a threshold value
for the hepatotoxic effect of styrene was calculated to exist when glutathione
content of the liver reached a level of 1 ijmol/gm tissue. Thus, glutathione
conjugation appears to offer significant protection against hepatotoxicity.
For many years it has been known that the metabolism of
ethylbenzene involves conversion to phenylacetic acid, 1-phenylethanol, man-
delic acid, and hippuric acid (Smith et. al., 1954; El Masri £t al., 1958). In
addition, more recent studies have shown that the benzylic hydroxylation of
ethylbenzene to optically active 1-phenylethanol occurs with a high degree of
stereoselectivity (McMahon and Sullivan, 1966; 1968). However, the complete
picture of ethylbenzene metabolism in mammals involves the participation of
acetophenone and its derivatives, particularly u-hydroxyacetophenone (Kiese and
Lenk, 1973; 1974). The sequential oxidation of ethylbenzene summarized from
studies conducted in vivo with rats indicated that the stereoselectivity of the
process is probably dependent on a keto reduction step involving u-hydroxy-
acetophenone or phenylglyoxal (Sullivan e_t ^1., 1976). The optical center of
155
-------
1-phenylethanol which is formed during the initial hydroxylation of ethyl-
benzene is probably destroyed by a subsequent dehydrogenation step to form
acetophenone.
The probable metabolic pathways involved in the biotrans-
formation of ethylbenzene are summarized in Figure 13. It is not likely that a
key epoxide intermediate is involved in ethylbenzene metabolism by mammals. It
was suggested, however, that the observed formation of 2- and 4-hydroxyethyl-
benzene from ethylbenzene in rats (Bakke and Scheline, 1970) may be due to
isomerization of the corresponding arene oxides (Kaubisch et al., 1972). These
are minor metabolites, however, accounting for only 0.3 percent of the admin-
istered dose (Bakke and Scheline, 1970).
c. Acute Toxicity
(1) Oral Administration
It has been known for many years that the acute oral
toxicity of styrene, ethylbenzene, and a-raethylstyrene is relatively low.
This observation is consistent with the reported oral toxicities of alkylated
benzenes in general. However, the acute lethal dose for the presumed styrene
metabolite, styrene oxide, is somewhat lower than for the parent hydrocarbon.
Table 35 summarizes the available published data on
the acute lethality of these compounds by oral administration. Pathologic
examination of treated animals revealed only slight liver changes and occa-
sional kidney involvement of questionable significance (Wolf et al., 1956).
Intoxication by a-methylstyrene was associated with general irritation, in-
coordination, tremor, convulsions, and hyperemia of the internal organs
(Korbakova and Fedorova, 1964). In addition, it was reported that styrene and
156
-------
Pheiiyacoturic Acid
O
^ /
C
I
CH2
"^
ni - Hydroxyacetophenone
0 CH,
CH,
CH,
1 — Phunylethannl
CH,
HO-C-H
-. Microsnines .
Eihylben/cne M I *- II
MICIOSOI UPS
CH2
CH,
CH,
CHOR
on
|i — Elhyl|)henol
R = Glucuronic 01
Siilfunc Acid
Phenylethylene
Glycol
OH
Acetophenone u — Hydroxyacetophenonc
O CH, Q.
OH
p — Hydi oxyaceluphennnc
Phenylylynxylic
Acirl
ALIC!
Figure 13. Probable Metabolic Pathways in the Biotransformation of Etrhylbenzene
-------
Table 35. Experimental Acute Oral Toxicity of Styrene and Derivatives
Ln
00
Compound
Styrene
Styrene
Styrene
Styrene
Styrene Oxide
Ethylbenzene
Ethylbenzene
Ethylbenzene
a-Methylstyrene
a-Methylstyrene
a-Methylstyrene
a-Methylstyrene
Species
rat
rat
rat
rat
rat
rat
rat
rat
rat
mouse
mouse
mouse
Sex & (No.)
male & female (57)
7
(59)
(59)
male
male & female (57)
7
male
male (20)
7
7
Dose
5 g/kg
8 g/kg
1.6 g/kg
8.0 g/kg
2.56 g/kg
3.5 g/kg
6 g/kg
-v-4.94 g/kg
4.9 g/kg
3 g/kg
5 g/kg
10.25 g/kg
Effect
Reference
LD (approx.) Wolf £t £l . , 1956
lethal concentration Faustov, I960
100% survival
100% mortality
LD n (approx.)
Spencer et al., 1942
Spencer et al., 1942
Weil et_ al. , 1963
LD (approx.) Wolf et_ aj.. , 1956
lethal concentration Faustov, 1960
LD (range =4.61
30 - 5.31 g/kg)
LD5Q (approx.)
30% mortality
LD50
Smyth et_ al. , 1962
Wolf et. aj.. , 1956
Korbakova & Fedorova, 1964
Ogleznev, 1964
Ogleznev, 1964
-------
a-methylstyrene, upon oral administration to mice and rats, caused hemodynamic
and dystrophic changes in the parenchymatous organs (notably the lungs), with
further morphological changes in the central nervous system characteristic of
toxic encephalopathy (Zakharchenko, 1969; Veselova and Ogleznev, 1965). It is
evident that species susceptibility (i.e., rats versus mice) may be a signifi-
cant variable in the interpretation of acute toxicity data.
(2) Vapor Inhalation
Experiments conducted with animals acutely exposed to
vapors of styrene, ethylbenzene, or a-methylstyrene indicate that the alkylated
benzenes are not highly toxic. Once again, however, species susceptibility is
likely to be an important factor in characterizing lethal dosage levels. Table
36 summarizes data from various studies involving single inhalation exposures.
Response to styrene vapors is usually rapid, but
dependent on the severity of exposure. Rats and guinea pigs exhibit eye and
nose irritation (lachrymation, salivation, nasal discharge, violent scratching)
at styrene concentrations up to 1300 ppm, which is followed by general weakness
and unsteadiness after 12 to 30 hours of exposure (Spencer et al., 1942).
Marked debilitation and occasional loss of consciousness results from 24 to
30 hours of exposure at levels of 2000 ppm. At 2500 ppm, weakness and stupor,
followed by loss of equilibrium, tremors, and unconsciousness, develop within
10 to 12 hours of exposure. At 5000 ppm, reaction to styrene is immediate and
involves loss of equilibrium, tremors, clonic convulsions, and unconsciousness,
usually within one hour. Deaths which occur from styrene exposure are gener-
ally due to action upon the central nervous system, although delayed deaths may
result from pneumonia which is secondary to acute lung irritation (Spencer
^t al., 1942). Jaeger and coworkers (1974) attributed death in rats from
159
-------
Table 36. Experimental Acute Inhalation Toxicity of Styrene and Derivatives
Compound
Species Sex & No. Dose
Effect
Reference
OS
O
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
rat ?
rat ?
mouse ?
rat ?
guinea pig ?
rat &
guinea pig
mouse
mouse
rabbit
Styrene Oxide rat
11.8 mg/Jl (2770 ppm)
x 4 hours
2700 ppm x 4 hours
21.0 mg/£ (4930 ppm)
x 4 hours
1300 ppm
1300 ppm
10,000 ppm
^3522 ppm x 2 hours
^2348 ppm x 2 hours
^9391 ppm x 2 hours
1000 ppm x 4 hours
(confidence limits
= 10.3-13.5 mg/J.)
LC50
LC,-n (confidence limits
= 17.8-24.8 rag/A)
100% survival with 30
hour exposure; 100%
mortality with >40
hour exposure
100% survival with 16
hour exposure; 100%
mortality with 40 hour
exposure
100% survival with 1
hour exposure; 100%
mortality with 3 hour
exposure
30% mortality
20% mortality
abnormal electroen-
cephalograms which per-
sisted for <_60 days
death in 2 of 6 animals
Shugaev & Yaroslavl, 1969
Jaeger et al., 1974
Shugaev & Yaroslavl, 1969
Spencer ^t al., 1942
Spencer et al., 1942
Spencer et_ al., 1942
Blinova & Rylova, 1957
Blinova & Rylova, 1957
Budko & Pankovets, 1968
Weil et al., 1963
-------
Table 36. Experimental Acute Inhalation Toxlclty of Styrene and Derivatives (Cont'd)
Compound
Species Sex & No. Dose
Effect
Reference
Ethylbenzene rat
Ethylbenzene rat
Ethylbenzene mouse
Ethylbenzene rat
a-Methylstyrene mouse
a-Methylstyrene rat
a-Methylstyrene mouse
a-Methylstyrene rat
a-Methylstyrene rat
6
7
VL3.367 ppm x 2 hours LC
^16,122-17,273 ppm x
2 hours
^8176 ppm
4000 ppm x 4 hours
^83 ppm x 2 hours
^621-1035 ppm
^621 ppm x 3 hours
^1035 ppm
ppm
50
100% mortality
LC50
50% mortality (3/6)
no effect seen
decreased acetylcholine
level in blood, kidneys,
and liver
Tvanov, 1962
Ivanov, 1962
Faustov, 1958
Smyth ££ al., 1962
Korbakova & Fedorova, ]964
Klimina, 1974b
accumulation of ammonia Solov'ev, 1969
in the brain, reaching
2.8 times normal level
within 11-20 days follow-
ing exposure
increased serum vitamin Moch'kina & Bravve, 1969
812 level by >140%, due
to liver damage
reduced brain tissue
respiration by >50%
Solov'ev, 1969
-------
styrene inhalation to pulmonary irritation and edema. No difference in LC,.-
concentrations was found when fasted or fed animals were used. Thus, the
presumed reduction of hepatic glutathione levels by fasting did not enhance the
toxic effects of styrene.
Target organs for acute styrene action are mainly the
central nervous system, hematopoietic system, liver, lungs, and kidneys (Spencer
eit, a^., 1942; Pokrovskii, 1961). Pulmonary lesions are the predominant patho-
logic features of acute intoxication, varying from slight congestion to severe
irritation with edema, exudation, hemorrhage, and leukocyte infiltration
(Spencer et al., 1942). Guinea pigs were apparently more susceptible to
pulmonary damage. Lesions of the liver and kidneys were encountered only
occasionally and were usually neither severe nor persistent. Actions of
styrene on the hematopoietic system include decreases in erythrocytes, throm-
bocytes, and hemoglobin (Pokrovskii, 1961).
Acute exposure to vapors of ethylbenzene are report-
edly associated with coordination disorders, narcosis, convulsions, pulmonary
irritation, and conjunctivitis (Ivanov, 1962). It is probable that the toxic
mechanisms for styrene and ethylbenzene are qualitatively similar. Ethyl-
benzene is apparently less potent than styrene in causing death by inhalation,
however.
The toxic action of a-methylstyrene when inhaled is
similar to that of styrene and ethylbenzene. Degenerative changes of the
cardiac muscle, liver, and kidneys have been reported (Blinova and Rylova,
1957). In addition, acute exposure to a-methylstyrene vapors can interfere
with normal protein anabolisra in the brain (Solov'ev, 1969) and alter blood and
tissue levels of acetylcholine, acetylcholinesterase, and butyrylcholinesterase
(Klimina, 1974a,b).
162
-------
(3) Skin Contact
Single skin application of styrene to the ear of a
rabbit produced no appreciable reaction (Spencer et^ al^. , 1942). However,
Blinova and Rylova (1957) reported that styrene and a-methylstyrene, when
applied undiluted to the skin of animals, caused necrosis. Moreover, two
applications of styrene on the shaven abdomen of rabbits produced marked irri-
tation and some denaturation (Spencer et al., 1942). In guinea pigs and rab-
bits, a-methylstyrene was reportedly highly sensitizing and slightly irritating
(Cirstea e£ al., 1966).
Ethylbenzene was shown to produce moderate irritation
to the uncovered belly of rabbits (Smyth et_ al., 1962), and also to intact and
abraded rabbit skin under 24-hour occlusion (Opdyke, 1975). Smyth and co-
workers (1962) reported a single skin penetration LD5Q value for ethylbenzene
in rabbits to be 17.8 ml/kg.
(4) Eye Contact
Wolf and coworkers (1956) determined the eye injury
potential of styrene, ethylbenzene, and a-methylstyrene in rabbits. Two drops
of the undiluted material were applied to the rabbit's eye, and observations of
resulting injury made periodically for seven days. Their results are summar-
ized in Table 37.
(5) Other Routes
Parenteral administration of styrene to male and
female rats has been used to compare its toxicity with that of the presumed
metabolite, styrene oxide (Ohtsuji and Ikeda, 1971). As Table 38 indicates, a
sex-related difference in susceptibility to either compound does not appear to
exist. However, it is clear that styrene oxide is considerably more toxic than
163
-------
Table 37. Irritation and Injury to the Eyes of Rabbits Caused
by Contact with Undiluted Materials3
Eye Response
Material
Ethylbenzene
Styrene
a-Methylstyr ene
Conjunctival Irritation0
Slight
Moderate
Slight
Corneal Injury0
None
Slight, transient
None
Modified from Wolf et_ al,., 1956.
The degrees of irritation were defined as follows:
slight=perceptible irritation of the conjunctival membranes
moderate=inflamination and slight swelling of the eyelids
The degrees of corneal injury were defined as follows:
very slight=questionable or just perceptible superficial necrosis in very
small areas of the cornea
slight=perceptible superficial necrosis involving less than 50% of the
cornea
moderate=definite superficial necrosis over more than 50% of the cornea
164
-------
Table 38. Intraperitoneal LD5_ Values for Styrene
and Styrene Oxide in Ratsa>b
Sex
Male
Female
Expt.
No.
1
2
1
2
Compounds
Styrene
(g/kg)
2.36
2.15
2.86
2.41
tested
Styrene oxide
(g/kg)
0.61
0.46
0.50
0.61
aOhtsuji and Ikeda, 1971.
Based on deaths occurring within 48 hours of treatment.
165
-------
styrene when administered by injection. These results would indicate, there-
fore, that the acute toxicity of styrene is probably mediated by styrene itself
and not by formation of the epoxide metabolite.
The effects of styrene on central nervous system
function in rabbits have been studied by Larsby and coworkers (1978). A 10%
styrene emulsion was infused at a constant rate into the jugular vein, and
arterial and cerebral spinal fluid (CSF) levels were monitored. Animals were
tested for both positional and rotatory nystagmus responses (involuntary eye
movements) as a measure of vestibular and oculomotor central nervous system
function. At levels of 40 ppm arterial styrene, or approximately 2 ppm CSF
styrene, a positional nystagmus was elicited that was not seen in controls.
In addition, at comparable styrene levels a reversal of rotary nystagmus was
noted. The authors commented that this reversal is an unusual effect which, to
their knowledge, has not been noted with any other compound tested.
The aspiration hazard toxicity of petroleum distillates
is an important consequence of accidental ingestion. Gerarde (1963) surveyed a
large number of hydrocarbons for their aspiration toxicity in male rats. He
found that instillation of 0.25 ml of ethylbenzene into the lungs of rats
caused central nervous system stimulation, cardiac arrest, respiratory paraly-
sis, and immediate death; this is comparable to the toxicity of benzene and
toluene administered by the same route.
A technique using the chick embryo as a test system
has been used to determine the relative toxicities of volatile chemicals
(McLaughlin e£ al., 1964). Among the chemicals tested for their ability to
prevent the hatching of fertile chicken eggs (acetone, allyl alcohol, benzene,
butyl acetate, o-butyl alcohol, carbon tetrachloride, dimethylformamide, ethyl
166
-------
acetate, ethyl alcohol, isoamyl alcohol, isopropyl alcohol, methanol, styrene,
and toluene), styrene was second in toxicity to allyl alcohol. A dose of
18 mg styrene injected per egg completely inhibited hatching.
d. Subchronic Toxicity
(1) Oral Administration
Among the earliest investigations on the toxicity of
styrene by repeated oral administration is the work of Spencer and coworkers
(1942) using male rats. Doses of 2000, 1000, 500, and 100 mg/kg were admin-
istered five days per week for four weeks. At the lowest dosage, all five rats
survived the treatment with no apparent toxic effects and with no significant
lesions at autopsy. At the 500 mg/kg dose level, reduced weight gains were
evident. At the two highest dosages, a few deaths occurred which were attribu-
ted to severe irritation of the esophagus and stomach.
Subsequent studies involving repeated feedings of
styrene were conducted with female rats (10 per group) given doses of 66.7 to
667 mg/kg five times per week for six months (Wolf e£ al., 1956). Additional
groups of rats were also treated with ethylbenzene at doses up to 680 mg/kg
using the same treatment schedule. The results of these studies are summarized
in Table 39. Only ethylbenzene induced histopathologic lesions. These con-
sisted of cloudy swelling in hepatic parenchymal cells and renal tubular
epithelium. Although hematologic parameters were evaluated (total erythrocytes
and leukocytes, hemoglobin content, white blood cell count), neither compound
produced any changes when compared to control animals.
A more recent report abstracted from the Russian
literature indicates that when styrene is fed to rabbits at doses up to
250 mg/kg for up to 216 days, the immunological defense system is severely
167
-------
Table 39. Summary of Repeated Oral Feeding of Styrene and
Ethylbenzene to Female Rats3
Material
Dose,
mg/kg/day
Feedings,
No.
Experimental
Period,
Days
Effects
Ethylbenzene
13.6
136
408
680
130
130
130
130
182
182
182
182
No effect
No effect
Lw+ and Kw+; Lp-f and Kp+
Lw+ and Kw+; Lp+ and Kp+
00
Styrene
66.7
133
400
667
132
132
132
132
185
185
185
185
No effect
No effect
G+; Lw+ and Kw+
G-H-; Lw-H- and Kw+
Modified from Wolf ejt a_l. , 1956.
DL=liver
K= kidney
G=growth depression
w=average weight
p=histopathology
+=slight effect
-H-=moderate effect
-------
impaired (Sinitskii, 1969). The blood complement titre was reduced and leuko-
cyte phagocytic activity was depressed.
It was reported that oral administration of 0.005 or
0.5 mg/kg of a-methylstyrene for periods of 20 to 140 days produced no perma-
nent changes in experimental animals (species not indicated) (Ogleznev, 1969).
(2) Vapor Inhalation
Extensive studies were conducted many years ago at the
Dow Chemical Company on the inhalation toxicity of styrene, ethylbenzene, and
a-methylstyrene to rats, guinea pigs, rabbits, and Rhesus monkeys (Spencer
et al., 1942; Wolf et al., 1956).
Animals were exposed to styrene vapors for seven to
eight hours per day, five days a week, for up to six months. Maximum exposure
levels employed were 2000 ppm for rats, guinea pigs, and rabbits, and 1300 ppm
for monkeys. Routine hematologic and tissue examinations were conducted on
animals of all species tested. Results are summarized in Table 40. No exposure-
related deaths among rats resulted from any of the styrene concentrations
tested; however, eye and nose irritation were commonly encountered. Among the
guinea pigs exposed to styrene, 10% of those at the highest dose level died,
revealing severe lung irritation with congestion, hemorrhage, edema, exudation,
and a general acute inflammatory reaction. No lesions were found in other
guinea pig tissues. Rabbits and monkeys were generally unaffected by repeated
styrene inhalation and revealed no significant histopathologic lesions. The
hematopoietic system was also apparently unaffected by styrene exposure.
Repeated inhalation exposures to ethylbenzene produced
more severe reactions than exposures to similar concentrations of styrene (Wolf
e£ ad., 1956). Maximum concentrations employed were 2200 ppm for rats,
169
-------
Table 40. Results of Repeated Vapor Inhalation Studies on
Animals Exposed to Styrene3
Animal
Species
Rat
Guinea
Pig
Rabbit
Average
Vapor
Sex &
No.
Concentrations,
ppm
2,000
1,300
2,000
1,300
650
2,000
1,300
mg/£
9.3
6.0-6.3
9.3
6.0-6.3
3.0
9.3
6.0-6.3
Both
Both
Both
Both
Both
Both
Both
(25)
(50)
(12)
(94)
(24)
(2)
(12)
7 -Hour
Exposures,
No.
105
139
98
139
130
126
264
Duration of
Experiment,
Days
148
214
148
214
189
148
360
Effects13
Eye and nasal
irritation C++
Eye and nasal
irritation
Eye and nasal
irritation OH-
Eye and nasal
irritation G+
No effect
No effect
No effect
Rhesus
monkey 1,300 6.0-6.3 Both (4) 264
360
No effect
Modified from Wolf et^ a^., 1956.
G=growth depression
-t-slight
-H«=moderate
170
-------
1250 ppra for guinea pigs and rabbits, and 600 ppm for monkeys. Exposures
were conducted for seven to eight hours per day, five days a week. The apparent
no-effect level of exposure for physiological reactions was about 400 ppm for
rabbits, guinea pigs, and monkeys (Table 41). However, this concentration
proved somewhat detrimental to rats. At higher concentrations, histopathologic
lesions were evident in the liver and kidneys of rats (cloudy swelling) and in
the testes of rabbits and monkeys (degeneration of the germinal epithelium).
No effects were demonstrated on the hematopoietic system of any species.
Exposure to a-methylstyrene, under the same conditions
as for styrene and ethylbenzene reported above, indicated that a no-effect
level existed in the area of 200 ppm (Table 42) (Wolf e£ al., 1956). In con-
trast to the other two chemicals, however, a-methylstyrene produced significant
mortality at concentrations of 600 ppm (rabbit) and 3,000 ppm (rat and guinea
pig). Nevertheless, histopathologic lesions or hematologic alterations were
not reported.
The foreign literature contains numerous reports on
the toxicologic effects of styrene, ethylbenzene, and a-methylstyrene in
laboratory animals resulting from repeated inhalation exposures. These studies
are summarized in Table 43. For the most part, it is evident that metabolic
disturbances occur from exposure to styrene or a-methylstyrene, particularly in
the central nervous system. In addition, styrene appears to have an adverse
effect on the state of the immune system. Ethylbenzene, on the other hand, may
affect hematopoiesis during long-term exposures. The clinical significance of
these chemical-related disturbances is difficult to assess, however.
171
-------
Table 41. Results of Repeated Vapor Inhalation Studies on
Animals Exposed to Ethylbenzene3
NJ
Animal
Species
Rat
Guinea
Pig
Rabbit
Rhesus
monkey
Average
Vapor
Sex
Concentrations ,
ppm
2,200
1,250
600
400
1,250
600
400
1,250
600
400
600
400
mg/S,
9.5
5.4
2.6
1.7
5.4
2.6
1.7
5.4
2.6
1.7
2.6
1.7
M
Both
Both
Both
F
Both
Both
F
Both
Both
Both
F
7-Hour
Exposures,
No.
103
138
130
130
138
130
130
138
130
130
130
130
Duration of Effects
Experiment,
Days
144 C++; Lw+; Kw-H-; Lp+; Kp+
214 G+; Lw+; Kw+; Lp+; Kp+
186 Lw+; Kw+
186 Lw+; Kw+
214 G+
186 Lw+
186 No effect
214
186 Tp+
186 No effect
186 Lw+ Tp+
186 No effect
Wolf £t £l., 1956.
G=growth depression
w=weight
p=histopathology
L=liver
K=kidney
T=testes
The intensity of response is noted as follows:
^questionable
+=slight
-H-=moderate
-------
Table 42. Results of Repeated Vapor Inhalation Studies on
Animals Exposed to a-Methylstyrenea
Animal
Species
Rat
Guinea
Pig
Rabbit
Rhesus
monkey
f Wolf et
b „ — ,
Average Vapor
Concentrations,
ppm mg/S,
3,000
800
600
200
3,000
800
600
200
600
200
600
200
14.49
3.86
2.90
0.97
14.49
3.86
2.90
0.97
2.90
0.97
2.90
0.97
1956
Sex
Both
Both
Both
Both
Both
Both
Both
Both
Both
Both
F
Both
7-Hr.
Exposures,
No.
3-4
28
149
139
3-4
27
144
139
152
139
149
139
Intensity of
Duration of Effects
Experiment ,
Days
3-4 M4-H-
38 G+; Lw+; Kw+
212 Lw+; Kw+
197 No effect
3-4 M4-H-
38 G+; LvH-; Kw+
212 Lw+
197 No effect
212 G+; M+
197 No effect
212 No effect
197 No effect
response is noted as follows:
G=growth depression
w=weight
p=histopathology
L= liver
K=kidney
M=mortality
+=slight
++=moderate
-H-+=severe
-------
Table 43. Experimental Subchronic Inhalation Exposure to
Styrene, ot-Methylstyrene, and Ethylbenzene
Compound
Species Concentration Duration
Effects
Reference
Styrene
rat
Styrene
Styrene
Styrene
Styrene
rabbit
rat
rat
Styrene
ppm
rabbit VL1.7 ppra
. 1 ppra
ppm
"VL17 ppm
mouse, ^2.3 ppm
rat,
rabbit
5 hours daily
x 6 months
Reduced liver glycogen, albu- Zlobina, 1963
min-to-globulin ratio, and
blood pressure; increased
liver weights and altered
motor function.
2 hours daily
x 4 months
4 months
30 days
5 hours daily
x 14-30 days
Pokrovskii & Vulchkova, 1968
No effect on white blood
cells; toxic granulation
in neutrophils; decreased
hemoglobin levels; retarded
maturation of myeloid cells.
Increased B-lipoprotein,
cholesterol, lecithin, and
nitrogen in the blood.
Decreased brain levels of
glutamic acid, serine, and
threonine; increased brain
glycine levels.
Increased brain levels of
free glutamate, histidine,
citrulline, asparagine,
serine, proline, methionine,
and leucine.
up to 4 months Disturbances of phagocytic Kazakova, 197la
mechanisms in the destruction
of bacteria and assimilation
of debris.
Pavlova & Agamova, 1974
Aliev & Gadzhiev, 1973
Gadzhiev & Aliev, 1974
-------
Table 43. Experimental Subchronic Inhalation Exposure to
Styrene, a-Methylstyrene, and Ethylbenzene (Cont'd)
Compound
Species Concentration Duration
Effects
Reference
Styrene
Styrene
rabbit ^6.8 ppm
rabbit ^37-47 ppm
Styrene
Styrene
Styrene
a-Methyl-
styrene
a-Methyl-
styrene
rat
rat
rat
rat
MJ.2 ppm
rabbit ^235 ppm
4 hours daily
x 4 months
4 hours daily
x 4 months
at 30-32°C
4 hours daily,
5 times per
week x 1-4
months
7 hours per
day
Decreased phagocytic activity Bekeshev, 1974
of the leukocytes and the
complement titre in the serum.
Decreased immunobiologic Samedov et al., 1974
reactivity; decreased levels
of albumins and increased
levels of Y~gl°bulins in
serum.
Lowered neutrophil phagocytic Kazakova, 1971b
activity and greater suscep-
tibility to staphylococcal
infections.
Blinova & Rylova, 1957
Vl or 12 ppm 1-4 months
Izyumova et al., 1972
^•10.3 ppm
4-5 hours
daily x 6
months
Increase in abnormal pseudo-
sinophils, monocytes, and
reticulocytes.
Changes in duration of the
estrous cycle.
Increased degradation and Solov'ev, 1974
deamination of brain proteins;
uncoupling of oxidative phos-
phor y la t ion in the brain
J. 3-14. 5 ppm 1-4 months
Increased acetylcholine in
the brain and kidneys and
decreased acetylcholine in
the blood and liver during
the first month; decreased
acetylcholinesterase in the
blood and spleen.
Klimina, 1974a
-------
Table 43. Experimental Subchronic Inhalation Exposure to
Styrene, a-Methylstyrene, and Ethylbenzene (Cont'd)
Compound
a-Methyl-
styrene
a-Methyl-
styrene
a-Methyl-
styrene
a-Methyl-
styrene
a-Methyl-
styrene
a-Methyl-
styrene
a-Methyl-
styrene
Species Concentration Duration
rat ^0.54 ppm 6 hours per
day x 120 days
rat VL-20 ppm 120 days
rat ^1.2 ppm 6 hours per
day, 6 days
per week x
4 months
rat ^10.3 ppm "chronic"
rat ^621 ppm 3 hours per
day x 100 days
rat ^2.1-8.3 ppm 5 hours per
day x 7 months
rat ^1 ppm 6 hours per
day x 120 days
Effects Reference
Vascular disorder in the Zakharchenko, 1969
brain stem and damage to
neurons and neuroglia.
Altered lipid metabolism; Chukreev, 1969
increased liver cholesterol
from 119 to 246.2 rag %.
Damage to respiratory Kuz'min, 1969a, 1969b
epithelium; hypersecretion
of epithelial mucins; damaged
blood vessel permeability.
Increased erythrocyte volume Mochkina & Bravve, 1969
by 11-37% and increased
hemolysis .
Abscesses of lung and hypo- Blinova & Rylova, 1957
dermic tissue; pneumonia, and
splenic hyperplasia in rats
on a protein and vitamin-
deficient diet.
Lowered urine volume and Korbakova & Fedorova, 1964
increased urinary protein;
hyperplasia of lymphatic
follicles; increased number
of lung histiocytes; peri-
vascular histiocyte infiltra-
tion; lipid -dystrophy in the
liver.
Inhibition of lymphopoiesis. Molodyuk, 1969
-------
Table 43. Experimental Subchronic Inhalation Exposure to
Styrene, a-Methylstyrene, and Ethylbenzene (Cont'd)
Compound
Species Concentration Duration
Effects
Reference
Ethylbenzene rabbit ^230 ppm
4 hours per Muscle chronaxia changes; Ivanov, 1964
day x 7 months disturbed blood cholinesterase
activity; decreased plasma
albumin; increased plasma
globulins; leukocytosis; reti-
culocytosis; cellular infiltra-
tion; lipid dystrophy in the
liver; dystrophic changes in
the kidneys.
-------
(3) Skin Contact
Repeated skin contact with styrene, a-methylstyrene,
or ethylbenzene is not well-tolerated in experimental animals. Ten to twenty
applications of either styrene or ethylbenzene to rabbits' skin caused a
definite erythema with development of a thin layer of devitalized tissue (Wolf
et al., 1956). A similar treatment using a-methylstyrene produced a more
morbid erythema, also accompanied by slight tissue necrosis. Absorption of
these compounds through the skin in amounts sufficient to be acutely toxic did
not occur.
A report on studies conducted in Russia (Mirzoyan and
Zhakenova, 1972) indicates that a-methylstyrene (30%) applied for twenty days
to rabbit skin resulted in inflammation, hyperemia, edema, and desquamation.
In addition, sensitization was reported.
(4) Parenteral Administration
Several reports abstracted from the foreign literature
suggest that subchronic administration of styrene by injection is associated
with disturbances in biochemical parameters of nervous system function and
possible effects on the liver. These studies are summarized in Table 44.
e. Teratogenicity
Studies concerning the embryotoxic and teratogenic potential
of styrene have only recently been conducted. No information is available con-
cerning the possible effects of a-methylstyrene or ethylbenzene on reproduc-
tion.
Investigators at the Dow Chemical Company treated groups of
pregnant female rats on days six to fifteen of gestation with styrene monomer
178
-------
Table 44. Subchronic Effects of Styrene Administered by Injection to Experimental Animals
Species
Dose
Route
Duration
Effect
Reference
Rat
vo
Rat
Rabbit
Rabbit
2.5 g/kg/day injection
2.5 g/kg/day subcutaneous
injection
600 mg/kg/day subcutaneous
injection
250 mg/kg/day intraperi-
neal injec-
tion
up to 20 days Suppression of serotonin Askalalonov, 1977
metabolism; decreased tissue
monoamine oxidase activity and
increased levels of cerulo-
plasmin; decreased excretion
of 5-hydroxyindale-3-acetic
acid.
15-20 days
3-10 days
until death
resulted
Decreased level of serotonin Askalonov, 1973a
in the blood, lungs, brain,
and intestine.
Increased activity of serum
cholinesterase and aryl-
esterase.
Increased serum levels of
globulin, glycoprotein, and
lipoprotein.
Askalonov, 1973b,c
Pannain & Scala, 1960
-------
by gavage (Murray ^t ^L., 1976). Styrene was administered twice daily in doses
of either 90 or 150 mg/kg, constituting a total daily dose of 180 or 300 mg/kg.
No evidence was obtained to indicate a styrene-related teratogenic effect. No
increases were seen in the incidence of skeletal or soft tissue abnormalities,
or in pregnancy rate, litter size, fetal body weight, or fetal viability. At
both dose levels, however, maternal toxicity was observed, which consisted of
weight loss and decreased food consumption. At the higher dosage, styrene
treatment produced focal ulceration in the gastric wall of pregnant rats.
The teratogenic effects of styrene and styrene oxide on
developing chick embryos has been studied by Vainio and coworkers (1977).
Styrene at 52-520 mg/egg and styrene oxide at 64-320 mg/egg were injected
into the air space of fertilized eggs on day zero and day one of incubation.
Embryos were examined on day 14 and scored for malformations. The average
incidence of malformations in styrene injected eggs was 15%, while for styrene
oxide injected eggs the average incidence was 7%. No malformations were
observed in vehicle injected controls. Malformations included a wide variety
of types with no single anomaly predominating. The significance of these data
is difficult to assess. At the higher concentrations of compound tested, levels
in excess of the LD-- value were being employed. Growth retardation observed
in treated embryos confirms the toxicity of this schedule. Since only average
incidence of malformations was presented, no correlation between dose and effect
can be made.
Fagano and coworkers (1978) have investigated the teratogenic
effects of styrene and styrene oxide on the developing sea urchin egg. Either
eggs or sperm were pretreated before fertilization for 1-2 minutes and then
extensively washed, or the fertilized eggs were treated at different stages of
180
-------
-4
in the continued presence of chemical. Concentrations of 10 M styrene resulted
in a 30% incidence of abnormal embryos. Styrene oxide at 10 to 10 M
concentrations also produced abnormalities of differentiation when given before
or after fertilization; no quantitative data were presented for the incidence
of these effects. The authors state that the effects seen resemble those pro-
duced by weak mutagens in this assay system.
Recently the results of studies conducted on rats and rabbits
to determine the teratogenic effects of styrene have been reported (Murray,
et al., 1978). Rats and rabbits were exposed to 300 and 600 ppm styrene vapor
for 7 hours/day during gestation (day 6-15 in rats, days 6-18 in rabbits).
Additional groups of rats were fed 90 or 150 rag/kg by gavage twice daily during
the same gestation interval. A few minor skeletal deformities (lumbar spurs,
delayed ossification) were seen in the rats exposed to 300 ppm, but not at the
600 ppm exposure level. At this level (300 ppm) rats also showed decreased
embryo length. Rabbits showed some delayed ossification at the 600 ppm exposure
level. No other deformities or reproductive effects were seen. Since rabbits
appear to be less sensitive to styrene inhalation than rats, studies at higher
levels may be indicated.
In contrast to these results, the Russian literature
contains a report of embryotoxic effects resulting from styrene inhalation
during the entire gestation period (Ragule, 1974). Exposure of pregnant rats
to approximately 0.4 to 12 ppm styrene four hours daily throughout gestation
caused a decreased number of offspring and a lowered viability of newborns.
The significance of exposure route in this study may be an important factor in
comparing these results to those reported by Murray and coworkers (1976).
181
-------
f. Mutagenicity
Significant concern regarding the safety of styrene has
arisen as the result of studies which indicated that styrene and its metabolites
possess mutagenic activity in certain test systems. By virtue of its biotrans-
formation to styrene oxide, a possible carcinogen (see Section III-B-2-g),
styrene has been considered as a likely candidate for mutagenicity testing.
Reports are now available on the mutagenicity of both styrene and styrene oxide
in eukaryotic and prokaryotic cell systems.
The simple Salmonella (+ microsome) microbial test for
mutagenesis has produced results which are somewhat difficult to interpret.
Styrene oxide has conclusively been shown to directly induce mutations in
tester strains which detect base-pair substitutions (Vainio et al., 1976;
Stoltz and Withey, 1977; Milvy and Garro, 1976) (Tables 45 and 46). In addi-
tion, styrene was reportedly not mutagenic to Salmonella in the absence of a
microsomal activating system (Milvy and Garro, 1976) (Table 45). Incubation of
styrene in the presence of liver microsomes, however, has produced both posi-
tive (Vainio et al., 1976; DeMeester e£ al., 1977) and negative (Stoltz and
Withey, 1977) results (Tables 47 and 48). The lack of mutagenic effect by
styrene in the presence of liver microsomes may have been due to poor conver-
sion of styrene to the epoxide and/or the rapid removal of styrene oxide once
it was formed. Nevertheless, it can be concluded from the work of Milvy and
Garro (1976) that the mutagenicity of styrene to Salmonella strains TA 1535 and
TA 100 is probably due to styrene oxide and not caused by other styrene metabo-
lites (Table 45).
Watabe and coworkers (1978) have studied increased muta-
genicity produced by styrene and styrene oxide under various conditions in the
182
-------
COMPOUND'
a
Table 45. Mutagenicity of Styrene and Its Metabolites
For Salmonella typhimurium^
Revertants per plate
TA1535 TA100
TA1537 TA1538 TA98
Styrene
Styrene oxide
Styrene glycol
D mandelic acid
L mandelic acid
Phenylglyoxylic acid
Benzyl alcohol
Benzoic acid
Hippuric acid
Spontaneous
61
535
93
106
153
162
177
101
186
135
268
2694
300
267
492
309
411
297
342
331
8
10
5
7
2
5
11
12
0
5
5
19
12
1
17
16
25
3
8
14
1
6
14
10
8
6
10
12
18
26
The test compounds were applied either as 5 ul of liquid (styrene, styrene
oxide and benzyl alcohol) or in approx. 100 yg amounts of solid to the center
of agar overlay plates seeded with the tester strains indicated. The sources
of the chemicals were: styrene and styrene oxide, Eastman Organic Chemicals;
styrene glycol, benzyl alcohol and hippuric acid, Biochemical Laboratories;
D and L mandelic acids and phenylglyoxylic acid, Aldrich Chemical Co.; benzoic
acid, Mallinckrodt Chemical Works. The styrene oxide is estimated by the
manufacturer, Union Carbide Chemical Corp., to be 97-98% pure.
Milvy and Garro, 1976.
183
-------
Table 46. Mutagenicity of Styrene Oxide to Salmonella Eyphimurium
( — indicates the absence and +
of S-9 per plate)3
Concentration of
styrene oxide
moles/plate
ID'4
ID'5
1C'6
_7
10 '
io-8
io-9
0
TA 1535 TA 1537
+ — +
toxic toxic
357 484 8 8
425 468 6 8
i_
249 N.D.b N.D. N.D.
124 N.D. N.D. N.D.
19 18 N.D. N.D.
20 45 74
TA
•~~
the presence
1538
+
toxic
11
7
9
5
7
9
32
35
16
12
9
7
TA
••—
of 0.1
100
+
toxic
1111
443
217
240
115
84
1165
639
146
142
108
135
ml
TA
— —
98
+
toxic
25
26
16
8
11
26
26
16
16
19
13
21
f Vainio e^ a^L., 1976.
No data
184
-------
Table 47. Mutagenicity of Styrene to Salmonella typhimurium
(- indicates the absence and + the presence of 0.1 ml
of S-9 per plate).3
Concentration of TA
styrene moles/plate -
lO'5
-6
10 °
_7
10 '
_«
10 °
0
1535
+
toxic
13
20
22
17
16
84
112
16
TA 1537
+
toxic
7
12
N.D.
7
11
12
N.D.
12
TA 1538 TA
+
100
toxic toxic
8 10 197
N.D.bN.D. 56
N.D. -N.D. 115
9 7 83
206
78
163
97
Ta 98
toxic
21
N.D.
N.D.
24
24
N.D.
N.D.
13
a Vainio e£ al_., 1976.
No data
185
-------
Table 48. Lack of Reversion of £. typhimurium TA1535 by Styrene in
the Presence of Different Amounts of Fortified Liver Homo-
genates from Arochlor 1254-pretreated Rats and Hamsters a
Treatment
20% EtOH
Styrene
500 ug/plate
DMSO
6-Naphthylamine
2 ug/plate
mg microsomal Revertants /plate
protein/plate Rat Hamster
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
12.3
14.0
16.0
12.3
8.3
9.3
15.0
15.7
10.7
5.7
6.7
7.7
13.3
226.3
284.7
168.0
16.3
15.6
11.0
12.0
9.7
10.7
12.7
10.0
12.0
6.0
5.0
7.3
11.3
137.3
75.7
56.3
a Stoltz and Withey, 1977.
186
-------
Ames assay. Styrene added to the test system at 10-500 mg/plate failed to induce
mutations in any tester strain when an S-9 microsomal extract prepared from the
livers of Aroclor treated rats was added. Styrene oxide increased mutations in
the Ames assay without S-9 activation at levels of 100 mg/plate and higher.
If S-9 extract prepared from phenobarbital or methylcholanthrene treated rats
was used, and an inhibitor of epoxide hydrase activity, trichloprene oxide
(TCFO) was included, Styrene added to the assay at 600 and 1200 mg/plate induced
a higher mutation rate in tester strain TA 100. Under these conditions methyl-
cholanthrene treated rats were the best source of S-9 liver preparation for
activation. Addition of this S-9 preparation to the Ames system (TA 100) con-
taining styrene oxide abolished the mutagenic activity of this compound. Further
addition of TCFO partially restored the mutagenic activity, indicating that
epoxide breakdown caused by the S-9 mix was a contributing factor to the lack
of activity noted. The authors speculate that since Aroclor treated liver pre-
paration is effective in converting styrene to styrene oxide but ineffective in
promoting styrene mutagenesis even in the presence of TCPO, another active
styrene metabolite is probably the mutagenic agent in this system. 4-Vinyl
phenol was tested for mutagenicity but was found to have a potent killing effect,
making evaluation of its effects not possible. Positive results observed should
be considered relative to the assay procedure. The activation of styrene using
S-9 mixture incubated for 20 minutes with TCPO was carried out by further incubation
with bacterial cells at 37° for 20 minutes in a shaker bath before addition to
agar and plating. This modification of the Ames procedure is more effective in
activating compounds that show borderline mutagenic activity than the standard
technique. Busk (1979) was unable to show mutagenic effects of styrene on
tester strains TA 100 and TA 1535 at concentrations up to 15 umoles/plate.
187
-------
Styrene oxide, at levels of 1-10 y moles/plate was mutagenic in both tester
strains. Aroclor or FCB induced microsome preparations did not activate
styrene and increase Salmonella mutations, nor did the further addition of
TCFO or diethyl maleate to the test system increase mutation rate. The standard
Ames technique was used for all testing. This group did not use TCFO addition
in the TA 100 strain assays because of reported high mutagenicity of this
compound itself for the TA 100 strain. Thus, comparison of the Watabe results
with those obtained by Busk is not possible.
Further studies conducted in test systems which employ
eukaryotic cells (yeast and hamster) have confirmed the mutagenic properties of
styrene oxide. Investigators in Italy (Loprieno et_ al., 1976a,b; Abbondandolo
e_t al., 1976) tested styrene and styrene oxide for their mutagenic effect on a
gene conversion system of yeast (£. cerevisiae), and on a forward mutation
system of Chinese hamster cells and yeast (£. pombe). Styrene was tested
either directly or after its biotransformation by liver microsomes in vitro or
by host-mediated metabolism in vivo. Styrene oxide was found to be active in
the production of forward mutations in both yeast and hamster cells (Tables 49
and 50). Styrene, on the other hand, was inactive in yeast, even in the pres-
ence of liver microsomes (Table 49). It was assumed that the conversion of
styrene to the epoxide was very low in this case. However, in the host-mediated
assay, both styrene (1000 ing/kg) and styrene oxide (100 mg/kg) were active in
the production of gene conversion (Table 51), but were unable to increase
forward mutation frequency in yeast cells (Table 52). By comparison with the
well-known mutagen ethylmethane sulfonate, the authors concluded that styrene
oxide was a more potent mutagen in the production of forward mutations in
cultured hamster cells. However, the high doses (1000 mg/kg) required for
188
-------
Table 49. Forward Mutations (ade Mutants) Induced in Yeast S. Pombe
00
VO
(Px Strain)3
COMPOUND mM
Styrene 100
(buffer)
100
(+ purified
microsome)
Styrene 5.0
oxide
10.0
15.0
20.0
Treatment
Time
0
60'
0
60'
0
60'
0
60'
0
60'
0
60'
Survival ^
% + S.E.M.
I
100.0
93.7
100.0
67.8
100.0
71.3 + 13.9
100.0
41.9 + 5.0
100.0
4.6 + 0.7
100.0
3.8
lumber of mutants
lumber of colonies
1/23,430
2/45,056
2/17,424
2/22,745
5/58,878
12/38,627
4/48,325
22/33,590
4/42,052
15/17,974
1/15,096
34/11,739
Mutants ade
4
10 colonies
0.43
0.44
1.14
0.88
0.85 +
3.17 +
0.82 +
6.86 +
1.02 +
8.31 +
0.66
28.96
0.06
1.04
0.16
3.34
0.28
0.02
Loprieno ej^ al., 1976a.
-------
Table 50. Forward Mutations (azg Mutants) Induced in Chinese Hamster Cells
(V,_ Strain)b»c
VO
o
COMPOUND mM3 Expression
concentration time of
plated cells
Styrene 0
8.5
17.0
Styrene 0
oxide , _5
8.50
17.0
25.0
66
90
72
72
90
90
P.E. (%)
100
83.7
77.4
89.8
72.4
57.4
14.9
20.0
azg
mutants
43(5)
11(2)
30(2)
61(13)
7(2)
53(3)
32(3)
91(1)
Viable cells
x 103
3746
1664
1394
12,177
1385
1721
263
200
azgr/106 cells + S.E.M.
11.37 +
13.14 +
20.56 +
4.94 +
5.09 +
29.97 +
139.96 +
455.00
2.35
0.32
11.14
1.22
0.95
11.32
28.32
Treatment, 60 min.
In parentheses the number of independent experiments.
Loprieno et al., 1976.
-------
Table 51. Mutagenicity Test With Host-Mediated Assay (Mice) : Gene Conversion
— ^
COMPOUND Dose Locus Incubation time (h)
0
Styrene Control ade 1.03 + 0.26xlO~
(6)b
_5
trp 0.51 + 0.17x10
(6)
1000 mg/kg ade
trp
Styrene Control ade 1.00 + 0.07x10
oxide (3)
-5
trp 1.30 + 0.28x10
(3)
100 mg/kg ade
trp
1
4.23 + 0.72xlO~5
(3)
1.94 + 0.25xlO~5
(3)
1.44 + 0. 08x10" 5
(3)
2.14 + O.lSxlO"5
(3)
3
4.75 + 0.64xlO~5
(6)
2.50 + 0.35xlO~5
(4)
1.42 + O.lSxlO"5
(3)
1.43 + 0.14xlO~5
(3)
6
0.92
(3)
1.37
(3)
5.38
(5)
2.64
(4)
1.18
(3)
0.91
(3)
2.29
(3)
1.84
(3)
+ 0.69xlO~5
_5
+ 0.73x10
+ 1.37xlO~5
+ 0.61xlO~5
+ O.llxlO"5
_5
+ 0.24x10
+ 0.53xlO~5
+ 0.27xlO~5
Treatment by gavage: 1 ml of DMSO solution.
Number of mice treated and analyzed.
Loprieno et al., 1976.
-------
VO
Table 52. Mutagenicity Test With Host-Mediated Assay (Mice) : Forward Mutation
(SL Pombe; ade Mutants; P.. Strain)0
COMPOUND
Styrene
Styrene
oxide
Dose Incubation time (h)
036
Control 1.20 + 0.20xlO~4
(6)b
1000 mg/kg 2.07 + 1.18xlO~4 1.67 + 0.54xlO~4
(4) (6)
Control 1.16 + 0.15xlO~4
(7)
100 mg/kg 0.96 + 0.05xlO~4 1.23 + 0.23xlO~4
(8) (9)
12
1.29 +
(4)
3.52 +
(8)
1.21 +
(3)
2.09 +
(6)
0.22xlO~4
1.21xlO~4
0.22xlO~4
0.49xlO~4
Treatment by gavage: 1 ml of aqueous solution.
Number of mice and analyzed.
Loprieno et al., 1976.
-------
styrene to exert a mutagenic effect implies that the degree of metabolic con-
version to styrene oxide is a limiting factor for mutagenesis.
Sorsa (1978) has made a preliminary report on the induction
of recessive lethal mutations in Drosophila following exposure to 100 ppm
styrene oxide vapor (duration not specified). Styrene oxide increased (9 fold)
the frequency of recessive lethals observed. Pretreatment with 1% phenobar-
bital for 24 hours followed by exposure to 100 ppm styrene oxide produced a
four fold increase in mutations over those produced by styrene oxide treatment
alone.
The mutagenic effects of styrene and styrene oxide have
been tested in onion root tip cells (Allium Cepa) (Linainman e£ al., 1978).
Application of equal amounts of styrene and styrene oxide solutions (0.05%)
to bulbs produced cytogenetic abnormalities. Styrene was more effective at
this level in producing chromosome breaks, while styrene oxide produced a
significant increase in cells with micronuclei. Both agents caused deconden-
sation of chromatin, suggesting an effect on chromosomal proteins. Autoradio-
graphy after exposure of bulbs to 7- H styrene oxide showed covalent binding
of the compound to both cytoplasmic and nuclear sites. Similar effects on
chromosomes of human lymphocytes cultured in vivo have been noted by these
investigators.
An increased incidence of chromosome aberrations has been
reported (Meretoga et al., 1978) in male rats exposed to 300 ppm styrene for
2-11 weeks (6 hrs/day, 5 days/wk). Aberrations seen were mainly chromo-
some breaks, but some chromatid breaks were also observed. These effects were
seen following nine weeks of exposure. Polyploid cells were observed in pre-
parations of bone marrow cells from animals exposed for eleven weeks. From
193
-------
nine to eleven weeks Che incidence of aberrations in styrene treated marrow
cells was 8-12% while controls showed a 1-6% incidence. Treated animals were
not followed after discontinuation of exposure to determine whether these changes
were readily reversible. Bonatti et al. (1977) has also noted polyploidy in
cultured V79 Chinese hamster cells exposed to styrene oxide.
No information is available in the published literature
concerning the mutagenicity of a-methylstyrene or ethylbenzene.
g. Carcinogenicity
The preliminary results of a single study have been reported
(Jersey et^ aJL., 1978) on the possible carcinogenicity of styrene. Rats of both
sexes inhaled styrene vapors (600 or 1000 ppm) six hours daily, five days per
week, for most of a two year period. Among the males a high mortality which
was unrelated to the styrene exposure prevented an accurate interpretation of
the data. Female rats, on the other hand, displayed an increase in tumors of
lymphatic or hematopoietic origin at both exposure levels.
The incidence of combined leukemia-lymphosarcoma in female
rats subjected to styrene at either 1000 ppm or 600 ppm exposure was ^ 7% (6/85).
Controls for this study showed a 1/85 occurrence of lymphosarcoma. Historial
analysis of leukemia-lymphosarcoma in female controls over a five year period
and comparison with styrene-treated female rats indicated a significant tumor
increase.
Results of the National Cancer Institute study on the
possible carcinogenicity of styrene administered by gavage to rats and mice
have been reported (NCI, 1979). Rats of both sexes were administered styrene
at levels of 2000 rag/kg and 1000 mg/kg, five days per week, for 78 weeks. An
additional group of rats was given 500 mg/kg styrene for 103 weeks, on the same
schedule. Male and female mice were administered styrene at levels of 300 mg/kg
194
-------
and 150 mg/kg for 78 weeks, five days per week. No statistically significant
increase in any tumor type was found for male or female rats, or female mice.
However, survival of both sexes of rats at the 2000 mg/kg level was low, and
early mortality makes analysis of tumor incidence in this group impossible.
Male mice showed an increased incidence of alveolar/bronchiolar carcinoma
and adema for animals treated with 300 mg/kg styrene. This incidence (9/43 or
20.9%) is significantly higher than for vehicle controls employed in the
study; however, historical controls with this strain of mice at the NCI
facility show spontaneous incidences of this type of tumor in the same fre-
quency range. Therefore, caution should be exercised in interpreting this
finding in one treatment group and one sex of test animals.
Limited studies have been conducted with mice to determine
the tumorigenicity of styrene oxide when applied to the skin. Weil e_t al.
(1963) observed no tumors among 40 12-week old C H mice painted with a 5%
solution of styrene oxide three times a week for life (17 to 24 months). When
a 10% styrene oxide solution was similarly applied, only two of 40 mice sur-
vived at 17 months, and no tumors were observed. Since styrene oxide is a
highly reactive electrophile, it will have a reduced probability of surviving
passage through the cytoplasm to reach critical cellular receptors which most
likely are in the nucleus. This factor may explain the negative results for
styrene oxide-induced skin tumors.
Among 30 8-week old male Swiss ICK/Ha mice painted with
0.1 ml of a 10% styrene oxide solution in benzene twice weekly for life, three
(10%) developed skin tumors (Van Duuren et^ al., 1963). The median survival
time for treated mice was 431 days. Among benzene-treated control mice 7% (11
of 150 animals) developed skin tumors.
195
-------
Kotin and Falk (1963) have reported a 16% incidence (3 of
20 animals) of malignant lymphoma among C~H mice painted with a total of 20 pm
styrene oxide. Nineteen of the mice survived the treatment, with the first
tumor appearing after 11 months. No tumors of other sites (skin, pulmonary)
were found in this study. Data were not given on the vehicle used for
administration of the test compound, the incidence of tumors among controls, or
the treatment schedule employed.
More recent evidence concerning the involvement of styrene
oxide with neoplastic transformation was reported by Nesnow and Heidelberger
(1976). In a cell culture transformation system using a C-H mouse embryo
fibroblastic cell line, styrene oxide caused a two-fold increase in 3-methyl-
cholanthrene-mediated transformation. Styrene had no effect on 3-methylchol-
anthrene-induced cell transformation (Table 53). The results indicated that
styrene oxide may increase chemical carcinogenesis by aromatic hydrocarbons due
to its ability to inhibit epoxide hydrase, a critical enzyme for the detoxi-
fication of carcinogenic arene oxide intermediates. Alternately, it was sug-
gested that styrene oxide may increase cellular steady-state levels of onco-
genic arene oxides by reacting with and thus depleting glutathione. The fact
that styrene did not alter the rate of transformation in this system argues
against the _in situ formation of styrene oxide in sufficient quantities to
affect transformation.
Information is not presently available regarding the
potential for neoplastic transformation by direct exposure to ot-methylstyrene
or ethylbenzene.
196
-------
Table 53. Effect of Modifiers of Microsomal Enzymes on 3-MC-Mediated Transformation
and Cytotoxicity in 10T1/2CL8 CellsS
Modifier
3-MC
(uM)
0
3.7*
Concen-
tration
(MM)
Start
treat-
ment*1
Length of
treat-
men te
PE3
30
30
% Survival
100
100
Transfor-
mation0
0
3.4
% Control
100
0
37
0
37
10
10
50
50
Styrene
-24 72
-24 72
-24 72
-24 72
Styrene oxide
13
12
12
9
65
60
60
45
0
8.1
0
7.2
108
96
0
37
37
50
50
50
0
0
-24
48
48
72
22
10
21
92
42
88
0
9.4
3.1
224
74
PE, percentage of the number of colony-forming cells, relative to the number of cells seeded.
Percentage of the ratio of the treated to control PE.
, Expressed as the number of transformed foci per dish, adjusted for PE.
Start treatment refers to the time (in hr.) that the chemical was added to the cells relative to the time
of 3-MC addition (zero time); thus, cells treated at -24 were treated 24 hr. prior to 3-MC addition.
Length of treatment is the total time (in hr.) that the cells were in contact with the chemical.
Cells were treated with 3-MC for 72 hr.
Modified from Nesnow and Heidelberger, 1976.
-------
3. Effects on Other Vertebrates
a. Fish
Both styrene and ethylbenzene have been tested for their
acute toxicity to various species of fish (Pickering and Henderson, 1966).
Static bioassays were conducted and median tolerance limit (TLM) values com-
puted from the mortalities in different concentrations of toxicant occurring
after 24, 48, and 96 hours of exposure. Bioassay results in four species of
fish are presented in Table 54. No explanation was given for the lack of
confidence limits for bluegills exposed to ethylbenzene.
A further analysis of the data obtained was made with
regard to potential for cumulative toxicity, comparative susceptibility of fish
species (Tables 55 and 56), and comparative toxicity in different dilution
waters. It is evident from these data that species susceptibility exists to
both styrene and ethylbenzene. Moreover, the toxicity of styrene was enhanced
when soft water was used for dilution. No significant differences for either
compound were found between the 24 and 96 hour TLM values.
No information has been found concerning the toxicity to
fish or other non-mammalian vertebrates by a-methylstyrene or divinylbenzene.
4. Effects on Invertebrates
No information is available for any of the compounds under
review.
5. Effects on Plants
No information is available for any of the compounds under
review.
198
-------
VO
Table 54. Median Tolerance Limits for Styrene and Ethylbenzene Obtained with the Moving
Average-Angle and Graphical Interpolation Methods3
COMPOUND
Styrene
(stabil-
ized
B.P.43-
45)
Ethyl-
(B.P.
134-136)
Dilu-
tion
Water
Soft
Hard
Soft
Soft
Soft
Soft
Hard
Soft
Soft
Soft
Test
Fish
24-Hr.
Confidence
TL Limits
48-Hr.
Confidence
TL Limits
96-Hr.
Confidence
TL Limits
(mg/1) (mg/1) (mg/1) (mg/1) (mg/1)
Fatheads
Fatheads
Bluegills
Goldfish
Guppies
Fatheads
Fatheads
Bluegills
Goldfish
Guppies
56.73
62.81
25.05
64.74
74.83
48.51
42.33
35.08
94.44
97.10
47.67-67.83
54.99-73.69
19.03-33.53
57.17-75.48
58.75-95.32
38.90-62.83
33.52-53.47
26.74-43.67
79.62-110.08
81.45-114.58
53.58
62.81
25.05
64.74
74.83
48.51
42.33
32.00
94.44
97.10
43.
54.
19.
57.
58.
38.
33.
32.
79.
81.
04-71.21
99-73.69
03-33.53
17-75.48
75-95.32
90-62.83
52-53.47
00-32.00
62-110.08
45-114.58
46.41
59.30
25.05
64.74
74.83
48.51
42.33
32.00
94.44
97.10
(mg/1)
37.11-59.
50.87-70.
19.03-33.
57.17-75.
58.75-95.
38.90-62.
33.52-53.
32.00-32.
79.62-110
81.45-114
Graphical Inter-
polation 96-Hr.
54
34
53
48
32
83
47
00
.08
.58
51
60
22
68
68
40
36
29
73
78
Modified from Pickering and Henderson, 1966.
-------
*a
Table 55. Comparison of Acute Toxiclty of Petrochemicals to Different Species of Fish
COMPOUND m (mg/1)
96-Hr TL and 95-Percent Confidence Limit for Organism
m (me/1)
Fatheads Bluegills Goldfish Guppies
Styrene 46.41(37.11-59.54) 25.05(19.03-33.53) 64.74(57.17-75.48) 74.83(58.75-95.32)
Ethylbenzene 48.51(38.90-62.83) 32.00(32/00-32.00) 94.44(79.62-110.1) 97.10(81.45-114.6)
*
Under standard conditions - soft water as diluent; temperature 25°C.
£| Modified from Pickering and Henderson, 1966.
o
-------
Table 56. Significance of Difference Between Estimated 96-Hr TL Values in Soft Water for Different
Species*a m
COMPOUND
Styrene
Ethylbenzene
Significance of Difference in 96-Hr TL
m
Fathead
vs.
Bluegill
0.13025
0.03298
Fathead
vs.
Goldfish
0.11454
0.27086
Fathead
vs.
Guppy
0.04466
0.27176
Bluegill
vs.
Goldfish
0.38559
0.37429
Bluegill
vs.
Guppy
0.32445
0.38083
Goldfish
vs.
Guppy
-0.10309
-0.09513
*
The 2 TL estimates will be judged significantly different if number is >0.
m
a
Modified from Pickering and Henderson, 1966.
-------
6. Effects on Microorganisms
Limited information has recently become available concerning the
effects of styrene and a-methylstyrene on algae, molds, and soil bacteria.
Using growth and vitality as parameters of a toxic effect, Munjko and Grbic*
(1977) examined numerous species of algae and molds exposed to these chemicals
in the nutritive media. Their results are summarized in Tables 57, 58, 59, and
60. It was apparent that styrene was the most toxic to algae, but neither
compound, when present at levels less than 0.5%, had a marked effect on algae
growth. Molds, on the other hand, were more sensitive to a-methylstyrene,
although concentrations required to inhibit growth were quite high (XL%). At a
level of 10% in the growth medium, a-methylstyrene completely inhibited mold
growth. It was not determined whether any of the test species of mold could
utilize styrene or a-methylstyrene as a sole carbon source.
Additional studies have been conducted with strains of Strepto-
mycetes isolated from soils and polluted river water to determine the effects
of styrene and a-methylstyrene on growth and physiologic characteristics
(Grbid and Munjko, 1977). Growth of streptomycetes on starvation media (agar
as only carbon source) was attained in the presence of styrene and a-methyl-
styrene at concentrations up to five and seven percent, respectively (Tables 61
and 62). None of the strains isolated from soils, however, were able to grow
in the presence of five percent test chemical. Further testing demonstrated
that both styrene and a-methylstyrene disturb streptomycetes homeostasis by
causing morphological alterations and an inhibition of the ability to decompose
macromolecules such as cellulose and gelatin.
A second series of experiments conducted by Grbic and Munjko
(1977) examined the ability of streptomycetes to utilize styrene and a-methylstyrene
202
-------
Table 57. Vitality and Growth of Algae in Water with Addition of Styrene3
Concentration of styrene in the medium
(% v/v)
species UL aj.gae
Chroococcus turgidus
Oscillatoria formosa
Nostoc entophytum
Anabaena augstumalis
Nitzschia palea
Chlamydomonas debariana var.
micropapillata •
Chlorella vulgaris var. vulgaris
Scenedesmus quadricauda
Pediastrum duplex var. rugulosum
Monoraphidium griffithii
Crucigenia triangularis
Hormidium flaccidum
Cosmarium laeve
0.01
R
R
R
R
R
R
R
R
R
R
R
R
R
0.05
R
R
R
R
R
R
R
R
R
R
R
R
R
0.1
R
R
R
R
S
R
R
R
S
R
R
R
R
0.5
S
S
S
S
S
S
S
S
0
S
S
S
S
R = normal growth, as with the control, S = stagnancy of growth, 0 = inhibition
of growth.
and Grbic, 1977.
203
-------
Table 58. Vitality and Growth of Algae in Water with Addition of Alpha-
Methylstyrene3
Species of algae
Chroococcus turgidus
Oscillatoria formosa
Nostoc entophytum
Anabaena augstumalis
Nitzschia palea
Chlamydomonas debariana var.
micropapillata
Chlorella vulgaris var. vulgaris
Scenedesmus quadricauda
Fediastrum duplex var. rugulosum
Monoraphidium griffithii
Cruclgenia triangularis
Honnidium flaccidum
Cosmarium laeve
Concentration of alpha-methylstyrene in the
medium (% v/v)
0.01
R
R
R
R
R
R
R
R
R
R
R
R
R
R = normal growth, as with the control, S =
0.05
R
R
R
R
R
R
R
R
R
R
R
R
R
stagnancy of
0.1
R
R
R
R
R
R
R
R
R
R
R
R
R
growth.
0.5
R
R
R
S
R
R
R
R
R
R
R
R
R
204
-------
Table 59. Growth and Changes in Pigmentation of Molds on
Sabouraud-agar with Addition of Styrene3
Concentration of styrene in the medium
(% v/v)
opecies or moj.as
Aspergillus niger
Aspergillus fumigatus
Aspergillus flavus
Collectrichum lindentia
Cephalosporium sp.
Fusarium sp.
Hypoxylon sp .
Penicillium notatum
Scopulariopsis sp.
Spicaria sp.
Trie hod erma lignorum
Trichothetium roseum
Verticillium sp.
0.1
4
4
4
4
4
4
4
4
4
4
4
4
4
0.5
4
4
4
3
4
4
3
4
4
4
4
3
4
1
4
3
3
1
3
3
2
3
2
2
2
1
2
5
3
1
3
0
1
2
0
2
0
0
0
0
1
10
1
0
1
0
0
1
0
1
0
0
0
0
0
4 = the growth as intensive as in the control, 3 = weaker growth and changes in
pigmentation, 2 = single, weakly pigmented colonies, 1 = tiny nonpigmented
colonies, 0 = inhibition of growth.
a Munjko and Grbic, 1977.
205
-------
Table 60. Growth and Changes in Pigmentation of Molds on
Sabouraud-agar with Addition of a-Methylstyrenea
Concentration of a-methylstyrene in the
medium (% v/v)
3pecj.es ui muj.ua
Aspergillus niger
Aspergillus fumigatus
Aspergillus flavus
Aspergillus candidus
Collectrichum lindentia
Cephalosporium sp.
Fusarium sp.
Hypoxylon sp.
Penicillium notatum
Scopulariopsis sp.
Spicaria sp.
Trichoderma lignorum
Trichothetium roseum
Verticillium sp.
0.1
4
4
4
4
3
4
4
3
4
4
4
4
4
4
0.5
4
4
4
3
1
3
3
2
3
2
2
3
3
3
1
3
2
2
2
0
2
1
0
2
1
1
1
1
2
5
2
1
1
0
0
0
0
0
1
0
0
0
0
1
4 = the growth as intensive as in the control, 3 = weaker growth and changes in
pigmentation, 2 = single, weakly pigmented colonies, 1 = tiny nonpigmented
colonies, 0 = inhibition of growth.
a Munjko and Grbic, 1977.
206
-------
Table 61. Growth of Streptomycetes on Mineral Agar with Addition of Styrene*
Percentage of strains on various concentrations
Habitat Growth of styrene (% v/v)
2 3 5 7 10
Soil
Water
Total
0
X
XX
XXX
0
X
XX
XXX
0
X
XX
XXX
15
25
40
20
0
60
20
20
12
32
36
20
40
45
10
5
20
60
20
0
36
48
12
4
100
0
0
0
40
60
0
0
88
12
0
0
100
0
0
0
100
0
0
0
100
0
0
0
100
0
0
0
100
0
0
0
100
0
0
0
a Grbid and Munjko, 1977.
0 = growth of the strains inhibited; X = the growth weaker than on the pure
mineral agar; XX = developed similarly as on the mineral agar; XXX = developed
more intensive than on the mineral agar.
207
-------
Table 62. Growth of Streptomycetes on Mineral Agar with
Addition of a-Methylstyrenea
Percentage of strains on various concentrations
Habitat Growth ot-methylstyrene (% v/v)
2 3 5 7 10
Soil
Water
Total
0
X
XX
XXX
0
X
XX
XXX
0
X
XX
XXX
60
20
20
0
20
0
40
40
52
16
24
8
95
5
0
0
20
20
20
40
80
8
4
8
100
0
0
0
20
20
20
40
84
4
4
8
100
0
0
0
60
0
0
40
92
0
0
8
100
0
0
0
100
0
0
0
100
0
0
0
3 Grbid and Munjko, 1977.
0 = growth of the strains inhibited; X = the growth weaker than on the pure
mineral agar; XX = developed similarly as on the mineral agar; XXX = developed
more intensive than on the mineral agar.
208
-------
as sole carbon sources. None of the strains isolated from soil were
able to grow in such a medium, and none of the strains were autotrophic (i.e.,
able to grow in a mineral solution without a carbon source). Nevertheless,
four (80%) of the strains isolated from river water grew on 2% styrene, one on
3% styrene, and one on 2% a-methylstyrene. The fact that streptomycetes taken
from polluted water were able to utilize styrene and to a lesser extent
a-methylstyrene as a sole carbon source indicates an adaptive mechanism for
habitats polluted with aromatic hydrocarbons.
In a single report abstracted from the Russian literature
(Zubritskii, 1962) it is stated that ethylbenzene at concentrations at or
exceeding 100 mg/fc adversely affected the growth of heterotrophic bacteria.
7. Biochemical Studies
Recent investigations at the biochemical level in mammalian
systems have provided important new data regarding the potential health effects
of exposure to styrene. Styrene given to rats by intraperitoneal injection for
three or six consecutive days (500 mg/kg/day) caused a doubling in the activity
of the xenobiotic hydroxylating enzyme p-nitroanisole 0-demethylase in the
liver (Parkki et al., 1976). The activity of aryl hydrocarbon hydroxylase, on
the other hand, was practically unaffected. A single dose of styrene at 2 g/kg
or repeated doses of 500 mg/kg nearly doubled the activity of epoxide hydrase.
Thus, it appeared that the capacity of the liver to transform the epoxide
metabolite of styrene to the less toxic glycol derivative may be enhanced with
chronic exposures. Moreover, exposure to styrene increased the rate of glu-
curonide conjugation and thereby accelerated the removal of potentially toxic
metabolic intermediates. In light of these results, it is not surprising that
styrene oxide cannot be detected as a metabolite in vivo.
209
-------
The importance of glutathione conjugation in the removal of
bioactivated chemical metabolites has prompted an examination of the effect of
styrene on the hepatic non-protein sulfhydryl content in mice, rats, hamsters,
and guinea pigs (Vainio and Makinen, 1977). When given single intraperitoneal
injections of styrene at 150 to 1000 mg/kg, a decrease in the hepatic non-
protein sulfhydryl content was evident in all species. However, this depletion
was most pronounced in mice (60% depletion) and much less so in rats (27%
depletion). These results lead to speculation that the formation of reactive
metabolites of styrene (i.e., styrene oxide) and their removal by glutathione
conjugation may be species dependent. This notion is supported by the obser-
vation that mouse liver has a high epoxide-forming and a low epoxide-inactivating
capability, thereby necessitating removal of epoxide intermediates by glutathione
conjugation. In this context it might be hypothesized that the rat may be much
less susceptible to the possible cytotoxic/carcinogenic actions of styrene than
is the mouse or other rodent species.
Recent work by Lambotte-Vandepaer and coworkers (1979) has indicated
that styrene administered intraperitoneally to rats will modify several liver
enzyme activities. Single styrene injections (10 mg/kg - 500 mg/kg) produced
altered (decreased) K values within 12-48 hours for the enzymes benzo(a)pyrene
m
hydroxylase, aldrin epoxidase, and styrene oxide hydrase. The K for styrene
epoxidase was unaffected. Ethylbenzene administered at 100 mg/kg had no signi-
ficant effect on the K of any of the four enzymes. Comparison of styrene effects
with those produced by methylcholanthrene (2 x 40 mg/kg) administered 24 and 48
hours prior to sacrifice showed a differential effect on styrene oxide hydrase,
since methylcholanthrene did not alter the K of this enzyme. A microsome-containing
m
fraction (S-9) prepared from the livers of rats pretreated with styrene
(500 mg/kg) or methylcholanthrene (2 x 40 mg/kg) at 24 hours, or 24 and 48 hours,
210
-------
before sacrifice enhanced the number of mutations produced by benzo(a)pyrene
(2.5-10 ug/plate) in the Ames test system. The authors postulated that this
enhancement of liver activity for activating mutagens is the result of
methylcholanthrene induction of benzo(a)pyrene hydroxylase, and of an
inhibiting effect of styrene on epoxide hydrase which would lower the overall
inactivation rate of potentially reactive species. These workers (Roberfroid,
et al., 1978) have shown that this same styrene pretreatment schedule (500 mg/kg)
increases the ability of liver (S-9) extract to activate acrylonitrile in the
Ames assay.
The perinatal development of epoxide hydrase and glutathione
transferase activities in the liver and at extrahepatic sites (liver, kidney,
lungs, intestinal mucosa) has been studied by Ryan et_ al. (1976) using
14
8- C-styrene oxide. All extra-hepatic tissues studied showed appreciable
glutathione transferase activity (rabbit, guinea pig). In the same species,
kidney and intestinal mucosa showed significant epoxide hydrase activity,
while very little activity could be shown in the lungs. Extra-hepatic
metabolic activity in the rat did not show the significant sex difference
observed for hepatic enzymes, except for lung epoxide hydrase. Perinatal
development of hepatic and extrahepatic glutathione transferase activity in
the rabbit proceeds at different rates; the liver activity develops more slowly.
The authors postulated that this different rate of transferase development
at various organ sites could affect the balance between conjugation and
hydration pathways for styrene oxide. Pretreatment of rats with phenobarbital
(3 x 80 mg/kg) for three days increased hepatic activities of glutathione
transferase and epoxide hydrase in both sexes. Dibenzanthracene given at the
same schedule did not induce either enzyme. Pregnenolone-16a-carbonitrile
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and tetrachloro-p-dioxin (TCDD) pretreatments of rats produced sex-related
differences in effects; female rats showed better induction of both gluta-
thione transfase and epoxide hydrase activities, although TCDD also elevated
male hepatic glutathione transferase significantly. Studies of styrene biotrans-
format ion in the isolated, perfused rat liver and rabbit lung showed glutathione
conjugate present in the bile and styrene glycol in the perfusate. Following
14
administration of 0.1 m mole of labelled (8- C) styrene oxide in the rat
liver system, 27-40% of the radioactivity was detected in the bile within 90
minutes indicating that conjugation with glutathione is a major pathway for
metabolism.
A dose-related covalent binding of styrene oxide to rat liver protein and
nucleic acids fractions has been reported by Marnicmi e£ al. (1977). Following
intraperitoneal injection of 7- H styrene oxide, covalently bound radioactivity
was found in both the total liver homogenate and the microsomal fraction.
Subsequent isolation of protein and nuclei acid fractions from the liver
indicated that as total injected styrene oxide was increased from 50 mg/kg to
200 mg/kg, the percent of bound radioactivity increased significantly (3-17 fold).
Incubation of these protein and nucleic acid fractions with styrene oxide in vitro
along with a microsomal fraction produced covalent binding. The addition of
10 mM glutathione to the reaction mixture decreased this binding by 80-90%.
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IV. Regulations and Standards
A. Current Regulations
1. Labelling Requirements
a. Styrene
The following label is recommended by the Manufacturing
Chemists Association (MCA, 1971):
STYRENE MONOMER
WARNING! CAUSES EYE IRRITATION
VAPOR IRRITATING
COMBUSTIBLE
Avoid contact with eyes.
Avoid breathing vapors.
Avoid prolonged or repeated contact with skin.
Keep away from heat and open flame.
Use with adequate ventilation.
Keep container closed.
Wash thoroughly after handling.
FIRST AID: In case of contact, immediately flush eyes
with plenty of water for at least 10 min.
Call a physician.
IN CASE OF:
Fire - Use foam, dry chemical, or C02-
Spill or Leak - Flush area with water spray.
MCA Chemical Safety Data Sheet SD-37 is available. Con-
tainers of styrene monomer must also bear the red "Flammable Liquid" sticker
(Sun Petroleum Products, 1975a).
b. a-Me thy 1 s tyr ene
An example of precautionary labeling for a-methylstyrene
is provided below (Union Carbide, 1975):
alpha-METHYLSTYRENE
WARNING! CAUSES EYE INJURY AND SKIN IRRITATION
Avoid contact with eyes, skin, or clothing.
Avoid prolonged or repeated breathing of vapor.
Use with adequate ventilation.
In case of contact with eyes or skin, immediately flush
with plenty of water for at least 15 minutes; for
eyes, call a physician.
FOR INDUSTRY USE ONLY
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c. Ethylbenzene
Precautionary labelling for ethylbenzene includes the red
"Flammable Liquid" label and the following warning (Sun Petroleum Products, 1975b)
ETHYLBENZENE
WARNING! FLAMMABLE
VAPOR HARMFUL
DANGER! HARMFUL OR FATAL IF SWALLOWED
Keep away from heat, sparks, and open flame.
Keep container closed.
Use only with adequate ventilation.
Avoid prolonged breathing of vapor.
Avoid prolonged or repeated contact with skin.
If swallowed, do not induce vomiting, call physician
immediately.
Keep out of reach of children.
Labels vary according to manufacturer, but the warning is essentially the same.
Tank cars and boxcars carrying ethylbenzene must bear the ICC "Dangerous"
placard (Charter Chemicals, no date).
d. Divinylbenzene
Divinylbenzene is considered a combustible liquid. Labelling
requirements and warnings are essentially the same as for other compounds.
2. Food Tolerances
Federal regulations regarding the use of styrene, a-methyl-
styrene, ethylbenzene, and divinylbenzene are primarily concerned with their
use as indirect food additives in the form of copolymers and polymers.
Regulations were found for the monomer styrene, divinylbenzene,
and a-methylstyrene. The use of styrene monomer in resinous and polymeric coat-
ings, and as an adhesive in articles intended for packaging, transporting, or
holding food (21 CFR 175.300; 21 CFR 175.105) was permitted. It was limited to
5% by weight of rubber articles intended for repeated use in food storage, handl-
ing, preparing, etc. (21 CFR 177.2600). Use as a solvent for inhibitors, accel-
erators, and catalysts used in the production of polyester resins for articles
214
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intended for food storage, handling, and preparation was also permitted (21 CFR
177.2420). Basic polystyrene polymers for use in contact with food may not
contain more than 1% by weight of total residual styrene monomer (21 CFR 177.1640),
Divinylbenzene is approved for use in ion-exchange resins; adhesives; paper and
paperboard in contact with aqueous, fatty, and dry foods; acrylic plastics; and
semirigid and rigid PVC plastics. a-Methylstyrene is approved for similar use
as well as for some rubber and sealing gasket applications (Burgess, 1978).
3. Standards for Human Exposure
a. Styrene Monomer
The U.S. Occupational Standard, time weighted average (TWA),
for air has been set at 100 ppm with a ceiling concentration of 200 ppra and a
peak concentration of 600 ppm/5 minutes/3 hours (EFA, 1976).
The Threshold Limit Value (TLV), established by the American
Conference of Governmental and Industrial Hygienists, is also 100 ppm or approxi-
•j
mately 420 mg/m (ACGIH, 1974, 1977). This level produced mild, transient
responses in 50% of the volunteers exposed.
The Soviet limit for exposure is 50 mg/m or approximately
12 ppm (ACGIH, 1974).
The American National Standards Institute also recommends
a TLV of 100 ppm and a ceiling value of 200 ppm (ANSI, 1968).
b. a-Methylstyrene
The U.S. Occupational Standard, TWA, for air and the TLV
have been set at 100 ppm or approximately 480 mg/m (EPA, 1976; ACGIH, 1974,
1977). This TLV will minimize complaints due to unpleasant odor and eye irri-
tation.
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c. Ethylbenzene
The U.S. Occupational Standard, TWA, for air and the TLV
have been set at 100 ppm or approximately 435 mg/m (EPA, 1976; ACGIH, 1974,
1977). Eye irritation will be minimal at this level.
d. Divinylbenzene
No recommended standards for human exposure are known.
4. NFPA Hazard Identification Code
The Hazard Identification System recommended by the National
Fire Protection Guide provides basic emergency information on health, flairana-
bility and reactivity. The NFPA symbol includes color and numerical codes as
follows:
Each diamond is assigned a number from 0-4,
ranging from 0 (no special hazard) to 4
(severe hazard or danger).
The NFPA symbols (NFPA, 1975) for the chemicals profiled in
this report are:
Styrene
Ethylbenzene Divinylbenzene a-Methylstyrene
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B. Current Handling Practices
1. Special Handling in Use
a. Styrene
Procedures for handling styrene monomer are explained by
the Manufacturing Chemists Association in Chemical Safety Data Sheet SD-37
(MCA, 1971). Normal practices associated with handling flammable organic
liquids should be employed.
Avoid breathing vapors, as well as skin and eye contact.
Special protective measures for use in handling styrene include: chemical
safety goggles; synthetic rubber boots if foot exposure is possible; gloves;
aprons; and face shields for complete face protection (MCA, 1971). Normal
ventilation is usually sufficient; however, if additional ventilation equip-
ment is installed, exhausts should be near the ground since the styrene monomer
is heavier than air.
Air or oxygen supplied masks are necessary during emergencies,
when the vapor concentration is greater than 2% by volume, when the oxygen level
is below 16% by volume, or exposure time is greater than 30 minutes (MCA, 1971).
Styrene is not compatible with alkylation catalysts, halo-
gens, hydrogen halides, sodium hydroxide, or glycols (which remove inhibitors),
and contact with these substances should be avoided (Monsanto, 1972).
b. a-Methylstyrene
a-Methylstyrene is also a combustible substance and should
be handled accordingly. When transferring liquids, the containers must be
grounded and bonded; containers should be opened with non-sparking tools
217
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(NIOSH-OSHA, 1975). Contact with oxidizing agents such as peroxides and
halogens may cause fire and explosions. To prevent hazardous polymerization,
avoid contact with peroxides, strong mineral acids, metal halides and similar
catalysts (Union Carbide, 1975). As with all flammable material, avoid high
temperatures and ignition sources.
Impervious clothing, rubber gloves, face shield, and
splash-proof goggles are necessary to protect the body during handling. Res-
pirators should be worn during non-routine activities and emergencies (NIOSH-
OSHA, 1975). Mining enforcement and administration approval is necessary for
respirators. Local exhaust ventilation is preferred in handling areas but a
general mechanical system is acceptable (Union Carbide, 1975).
c. Ethylbenzene
Ethylbenzene is a NFPA No. 30 Class 1C flammable liquid
(Shell, 1972). Contact with acid, metallic hydrides, and iron chlorides
should be avoided. Hazardous polymerization of ethylbenzene will not occur.
Contact with eyes or skin and breathing of vapors should
be avoided. Special protective equipment including rubber or plastic gloves
and goggles should be worn when handling ethylbenzene (Union Carbide, 1972).
Respirators are not required except in enclosed space where an air supplied
mask should be worn. A general mechanical ventilation system is acceptable
but a local exhaust is preferable.
d. Divinylbenzene
Divinylbenzene is combustible, and exposure to flame,
heat, or oxidizing materials should be avoided. Hazardous polymerization may
occur at high temperatures and pressures (Dow, 1977a).
218
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For exposure to levels up to 2% in air for one half hour
or less, a full face mask and organic vapor canister should be used (Dow, 1977)
Self contained breathing apparatus or equivalent is necessary during emergen-
cies. Safety glasses and body-covering clothing provide adequate body protec-
tion.
2. Storage and Transport Practices
a. Styrene
Styrene monomer is not regulated by the Department of
Transportation Hazardous Materials Regulations (MCA, 1971). It is considered
a Class 1C flammable liquid by the U.S. Department of Labor. Open flames,
local hot spots, friction, static electricity, and other ignition sources
should be avoided.
Storage tanks may be constructed of steel, black iron,
aluminum, and galvanized iron. Copper and copper alloys should not be used
as they are subject to attack by the styrene monomer itself and the organic
aldehydes and peroxides which may be present as contaminants. The tanks
should be electrically bonded and grounded against static electricity; in
addition, all electrical installations are subject to Article 500 of the
National Electric Code concerning hazardous fire and explosion areas.
Polymerization of styrene monomer occurs readily at ele-
vated temperatures and in the presence of both peroxides and strong acids.
An inhibitor such as 4-tert-Butylcatechol (TBC) is effective in controlling
polymerization. Because the inhibitor is consumed over time, periodic checks
must be made. If the monomer is stored at temperatures below 70°F, once a
week is sufficient. If, however, temperatures are greater than 70°F, a daily
219
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measure of inhibitor and polymerization should be made. TBC should be main-
tained at a level of at least 10 ppm. Dow (1967) recommends an inert gas
blanket to prevent polymerization in the uninhibited vapor area (above the
liquid level). Oxygen should not be entirely eliminated because TBC is in-
effectual in its absence.
For further information on storage and handling practices,
consult: "Storage and Handling of Styrene Type Monomers" (Dow, 1967) and
"Bulk Storage of Styrene Type Monomers" (Dow, 1961).
b. a-Methylstyrene and Divinylbenzene
Storage and handling requirements of ct-methylstyrene and
divinylbenzene are similar to styrene (Dow, 1967). Because divinylbenzene is
much less stable than styrene, TBC concentrations of 1000 ppm are necessary
for storage up to 30 days at temperatures less than 90°F. Refrigerated
storage and dissolved oxygen are required for effective inhibition of polymer-
ization. a-Methylstyrene is more stable than styrene; therefore, refrigeration
is not necessary.
c. Ethylbenzene
As with the other compounds, open flame, friction, static
electricity, and other sources of ignition should be avoided in storage and
handling.
Ethylbenzene is usually stored in carbon steel tanks (Union
Carbide, 1972). Tin, aluminum, and copper tanks may cause slight discoloration
with prolonged contact. Underground storage is recommended because of the
relatively low flash point of 84°F. If storage is to be above ground, a flame
arrestor in the vent line and inert gas blanketing are necessary.
220
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3. Accident Procedures
a. First Aid Procedures
(1) Styrene
Emergency first aid procedures for exposure to styrene
are from the NIOSH-OSHA Draft Technical Standards (NIOSH-OSHA, 1975) and the
Manufacturing Chemists Association (MCA, 1971).
If styrene gets into the eyes, irrigate with large
amounts of water for at least 15 minutes. Make sure the upper and lower eyelids
are occasionally lifted to facilitate proper cleansing. Call a physician as
soon as possible.
If styrene comes in contact with skin or clothing,
remove all contaminated clothing and flush the skin area with water. If irrita-
tion occurs, consult a physician.
Consult a physician immediately if ingestion of styrene
should occur. MCA recommends inducing the patient to vomit (except when un-
conscious), whereas NIOSH-OSHA states that vomiting should not be induced (MCA,
1971; NIOSH-OSHA, 1975).
If a person inhales large quantities of styrene, remove
him to fresh air and get medical attention as soon as possible. Oxygen may be
administered by qualified personnel.
First aid procedures for ethylbenzene, divinylbenzene,
and a-methy1styrene are similar to those given for styrene.
b. Spill and Leak Procedures
(1) Styrene
Small spills may be flushed with water or absorbed with
sand and removed in a container for disposal (Dow, 1977b). Large spills may be
diked, pumped with water, and then recovered for disposal or purification.
221
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Disposal of styrene wastes can be by incineration in
properly designed furnaces. Water may be purified by blowing the mixture
with air; the air may be burned if contamination is severe (MCA, 1971).
(2) a-Methylstyrene
Small spills can be absorbed with paper towels with
subsequent evaporation and burning of the paper. Large spills should be
collected with a vacuum truck and atomized in a combustion chamber (NIOSH-
OSHA, 1975). Disposal should be by incineration or tertiary waste treatment
(Dow, 1977c).
(3) Ethylbenzene
Flush small spill areas with water. Use of a vacuum
truck and incineration of waste are recommended for large spills (Shell,
1972).
(4) Divinylbenzene
Absorb small spills in sawdust or flush with water.
Dike and pump off large spills for incineration (Dow, 1977a).
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TECHNICAL SUMMARY
A group of four commercially related substituted benzenes have been con-
sidered in this review: ethylbenzene, the precursor of styrene, and three
vinyl substituted benzenes - styrene, a-methylstyrene, and divinylbenzene.
These compounds are colorless liquids which are fairly volatile (vapor
pressure ranges from 1.53 to 38.60 torr at 208C), water insoluble (at 25°C
water solubility of ethylbenzene is 161 ppm), and transparent to ultraviolet
light at wavelengths greater than 300 nm. Ethylbenzene is a stable chemical
while the styrene compounds are considerably more reactive, and commercial
products have to be stabilized with a polymerization inhibitor.
Ethylbenzene and the styrenes are very important commercial chemicals.
In 1976 the chemicals were produced in the following quantities (millions of
pounds) (USITC, annual a): ethylbenzene - 7,200; styrene - 6,301; a-methyl-
styrene - 61.4; and divinylbenzene - not available (in 1972 production was
3.4). These compounds are produced by a diverse group of petroleum and chem-
ical companies primarily located in Texas and Louisiana (SRI, 1977; Soder,
1977; Paul and Soder, 1977; and Chemical Prof., 1977c). Styrene oxide, a
commercial chemical that has not been treated in great detail in this review,
is produced in 1-2 million pounds annually (Soder, 1977). This small produc-
tion volume is significant because this styrene metabolite is mutagenic and
possibly carcinogenic.
Ethylbenzene is mostly produced by the liquid-phase, Friedel-Crafts
alkylation of benzene with ethylene using aluminum chloride as a catalyst
(Faith et_ al., 1975). Small amounts of ethylbenzene are also available by
fractionation of mixed xylenes. At many production facilities ethylbenzene
223
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is captively consumed in the vapor phase dehydration to styrene. a-Methyl-
styrene can also be made by dehydrogenation but it presently is produced as a
by-product from cumene-to-phenol processes. When cumene is converted to
phenol and acetone, a-methylstyrene represents about 1.7% of the total cumene
conversion. Divinylbenzene is produced by dehydrogenation of isomeric diethyl-
benzenes to form a mixture of components, chiefly divinylbenzene and ethyl-
vinylbenzene (Coulter e£ al., 1969).
There are other commercial processes where ethylbenzene or styrene are
formed. Ethylbenzene is found in the mixed xylene stream obtained by cataly-
tically reforming the naphtha stream of crude petroleum. Most of the cataly-
tic reformate is blended into gasoline. The catalytic reformate is a source
of approximately 10,000 million pounds per year of ethylbenzene, of which only
a small amount of ethylbenzene is actually isolated commercially. Another
non-commercial source of both ethylbenzene and styrene is pyrolysis gasoline
which is obtained when paraffins, condensates, naphtha, and gas oil are cracked
to produce ethylene. Pyrolysis gasoline provides about 57-96 million pounds
of ethylbenzene and 228-342 million pounds of styrene annually.
Ethylbenzene is used almost totally to produce styrene while the styrenes
are consumed totally in the production of plastics and rubbers. Approximately
97% to 98% of the ethylbenzene produced in the United States is consumed in
styrene production; 1% to 2% is exported and less than 1% is used as solvents
(Paul and Soder, 1977). The major consumption of styrene is for polystyrene
(straight - 28.5%, impact - 26.5), ABS resins (7%), SAN resins (1.5%), styrene-
butadiene copolymer latexes (6%), SBR elastomers (9.5%), and unsaturated poly-
ester resins (6.5%). These products are used in consumer products (toys,
224
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tires, furniture, appliances, carpeting, etc.) and construction and industrial
products (pipe, rubber products, paper coatings, ion-exchange resins, etc.)*
a-Methylstyrene and divinylbenzene are consumed in much smaller quantities,
mostly for specialty polymers and resins. a-Methylstyrene is widely used in
modified polyester and alkyd resin formulations as well as copolymers with
methylmethacrylate, low molecular polymers for plasticizers in paints, waxes,
etc. Its main use appears to be in ABS resins used in automobiles (Chem. Prof.,
1974a). Divinylbenzene is mostly used in the production of ion-exchange resins.
The sources of environmental release of ethylbenzene and the styrenes are
diverse and numerous and come from both commercial and non-commercial sources.
Losses during production can result from vents on distillation columns and
other process equipment, storage tank losses, miscellaneous leaks and spills,
process waste waters, and solid process waters. Styrene has been detected in
the vent emissions of petrochemical plants (Pervier et al., 1974) and in water
effluent from latex, textile, and chemical plants (Shackelford and Keith,
1976). One estimate of production loss of ethylbenzene was 1% of production
(Fuller e^ al., 1976) and it has been detected in several industrial chemical
plant effluents.
Since the end products of ethylbenzene and the styrenes are polymers, the
release of monomer should be small. However, as with all polymers, there is a
small residue of monomer as well as starting material ethylbenzene which is
found in the polymers. The concentration (wt %) of styrene and ethylbenzene
in various grades of polystyrene can vary from 0.04 to 0.32 and 0.05 to 0.09,
respectively (Crompton and Myers, 1968). Considering the production of poly-
styrene (3,200 million pounds in 1976) and assuming an average of 0.10 wt %
225
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styrene and 0.06 wt % ethylbenzene, polystyrene would contain 3.2 million
pounds of styrene monomer and 1.92 million pounds of ethylbenzene. Styrene
and styrene oxide have been detected in air samples taken inside reinforced
plastics (polyester) plants in Sweden (styrene 50-150 ppm; styrene oxide
0.03-0.2 ppm) (Pfaffli et al., 1979; Fjeldstad et al., 1979).
Environmental release from fuels, other petroleum processes, and combus-
tion sources may equal or exceed the loss from commercial sources. Ethyl-
benzene has been detected in automotive exhaust (0.51 volume %) (Schofield,
1974). If it is assumed that approximately 12.5 million tons of hydrocarbons
are emitted from motor vehicles (Council on Environmental Quality, 1975) and
ethylbenzene is about 0.60 volume %, then roughly 280 million pounds of ethyl-
benzene are emitted from motor vehicle exhaust each year (about 4% of the
total manufactured each year). Styrene has also been detected in hydrocarbon
exhausts from spark-ignition engines (Fleming, 1970) using high m-xylene fuel
compositions. In addition, styrene and methylstyrene have been identified in
oxy-acetylene and oxy-ethylene flames (Crittenden and Long, 1976), which
suggests that combustion sources may be a major environmental source of these
compounds. Styrene has also been detected in gas products from laboratory
pyrolysis of phenolic resin which are used in commercial brake linings (Fisher
and Neerman, 1966), and both ethylbenzene and styrene have been identified in
cigarette smoke (Johnstone e_t al., 1962). In addition, it is quite likely
that ethylbenzene and styrene may be released from cracking plants that pro-
duce ethylene.
The environmental fate of ethylbenzene and the styrenes has not been well
characterized but there is enough information to suggest some general processes.
Both ethylbenzene and styrene are stable enough to be detected in ambient air
226
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and water samples. Concentrations of ethylbenzene as high as 0.01 ppm have
been detected in 1961 (Altshuller and Bellar, 1963) in Los Angeles but more
recent values are around 1-5 ppb (Neligan ££3^., 1965; Bergert £t al^, 1974).
Styrene has also been detected at 0.2-5.0 ppb in urban air (Neligan et al.,
1965; Hoskeka, 1977). Both ethylbenzene and styrene have been detected in
finished drinking water (Shackelford and Keith, 1976) but little information
on concentration is available.
Although both these compounds have been detected in ambient air and water,
the information on their chemical stability would suggest quite different
rates of degradation. Styrene is a very reactive compound which in commercial
quantities has to be stabilized. Its odor threshold is low due to aerial
oxidation to aldehydes and ketones. In photochemical smog chamber studies,
styrene is rated as more reactive than the more reactive olefins but not as
reactive as ct-methylstyrene, which is ranked as one of the most reactive
chemicals (Levy, 1973; Laity ^t al., 1973; Darnall et al., 1976). The products
of photochemical oxidation have not been identified. In contrast to styrene,
ethylbenzene appears to be much less reactive under simulated atmospheric
conditions. Its reactivity is closer to toluene, and both have similar reaction
rates -with hydroxyl radical (Darnall et^ al., 1976). Hydroxyl radical reaction
rates appear to be indicative of atmospheric reactivity. Both ethylbenzene
and styrene are susceptible to metabolism by mixed cultures of microorganisms
in water systems, although only indirect analytical methods (CO. evolution and
BOD) were used (Ludzack and Ettinger, 1963; Price £t al^., 1974). A number of
investigators have determined the microbial pathways of ethylbenzene and a-
methylstyrene with pure cultures. Oxidation on both the ring and the side
chain were noted, and which process takes place is dependent upon the substitution
227
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on the side chain. The physical properties of the compounds under study suggest
that in trace quantities they are soluble in water; they will evaporate relatively
rapidly and will be found in a vapor state in the atmosphere; and they are not
likely to bioconcentrate in biological organisms because of their relatively high
water solubility.
The human health effects of styrene, a-methylstyrene, and ethylbenzene
are numerous and diverse. Most of the available health data are derived from
occupational studies of workers exposed to styrene (Zielhuis, 1964; Lorimer et_
al., 1977; Lilis et_ al., 1978; Lindstrom e£ al., 1976; Meretoja et_ al., 1977;
McMichael et al., 1976). However, concommitant exposure to other industrial
chemicals commonly occurs, which prevents a definitive judgement of the effects
of styrene alone. Nevertheless, it is apparent from many years of industrial
observation that styrene primarily produces irritation of respiratory and
conjunctival mucose at low levels of exposure O100 ppm) and narcosis at high
levels (>800 ppm) (Stewart e± al., 1968; Carpenter e£ al., 1944). Chronic
occupational exposures to styrene are associated with neurotoxicity involving
both the central nervous system and the peripheral nerves (Lilis et al.,
1978; Lindstrom e£ al., 1976; Seppalainen and Harkonen, 1976). Workers
exposed to a-methylstyrene and ethylbenzene experience symptoms qualitatively
similar to those produced by styrene, although no studies have been conducted
which are sufficiently validated to provide definitive dose- and time-response
data.
Limited epidemiologic evidence from workers in the styrene-butadiene
rubber industry has suggested an association between styrene exposure and an
excess incidence of leukemia and lymphoma (McMichael et_ al., 1976; National
Institute for Occupational Safety and Health, 1976). Thus far, sufficient
228
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data are not available to either confirm or deny the possible leukemogenic
properties of styrene. However, a recent study (Meretoja et^ al_., 1977) has
revealed an elevated incidence of chromosome abnormalities in the cultured
lymphocytes of ten chronically-exposed styrene workers. The identification of
styrene metabolites in the urine strongly suggested a causal relationship
between styrene absorption and chromosome damage. No information is available,
however, to indicate minimum levels and duration of exposure required to pro-
duce this clastogenic response.
Controlled studies with human volunteers have established that styrene
and ethylbenzene are readily absorbed across the respiratory epithelium and
the skin (Astrand e_t a_l. , 1974, 1975; Bardodej and Bardodejova, 1970;
Dutkiewicz and Tyras, 1967, 1968). In addition, it was shown that styrene
absorption via the lungs was a linear function of ventilation rate, and that
light exercise could produce a dramatic rise in styrene blood levels (Astrand
e_t al_. , 1975). Styrene and ethylbenzene are rapidly excreted in humans,
primarily as urinary mandelic acid (Astrand et_ a_!L., 1974; Bardodej and
Bardodejova, 1970). Significant retention of styrene and ethylbenzene vapor
may occur in the respiratory tract, and styrene can be detected in alveolar
air up to 24 hours after termination of exposure.
Experiments with laboratory mammals confirmed that styrene is rapidly
and extensively distributed throughout the body, regardless of the route of
exposure (Danishefsky and Willhite, 1954; Sauerhoff et^ al., 1976; Sauerhoff
and Braun, 1976). Furthermore, the excretion of styrene and its metabolites
is very rapid, with elimination being essentially complete within 72 hours
after exposure. However, patterns of styrene excretion appeared to be dose-
dependent, suggesting that saturation of metabolic pathways may occur at high
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doses and lead to qualitative and quantitative differences in biotransforma-
tion and elimination mechanisms (Sauerhoff and Braun, 1976).
As a result of dose-dependent metabolism as evidenced by studies with
styrene, an abnormal accumulation of certain bioactivated metabolites (pre-
sumably styrene oxide) may occur at doses which exceed detoxification capaci-
ties. At these doses, the risk of adverse physiologic reaction to a toxic
metabolite is greatly increased. In rats, it is suggested that such an accum-
ulation of activated styrene metabolites might occur at inhalation exposures
exceeding 600 ppm or oral doses of 500 mg/kg (Sauerhoff and Braun, 1976).
Indeed it has been shown that styrene absorption causes a dose-related depletion
of liver glutathione, an essential compound for the detoxification and removal
of bioactivated chemical intermediates, particularly epoxides (Vainio and
Makinen, 1977). However, since styrene-mediated glutathione depletion showed
considerable species variation, it is difficult to determine a specific level
of exposure likely to result in abnormal risk from toxic metabolite accumula-
tion. In addition, the possibility that chronic styrene exposure may enhance
the activity of styrene detoxification mechanisms such as epoxide hydrase
activity and glucuronide conjugation makes quantitative human risk evaluation
uncertain (Parkki £t_ al_. , 1976).
In examining the pathways of metabolism for styrene and ethylbenzene
particular attention has been paid to the possibility of epoxide formation.
Reactive epoxide intermediates are considered to be crucial determinants for
carcinogenicity and mutagenicity of aromatic hydrocarbons. In this regard
there are sufficient data to support the role of styrene oxide as an obligatory
intermediate in the metabolism of styrene in animals and man (Liebman, 1975;
230
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Liebman and Ortiz, 1969, 1970; Salmona et^ al_., 1976). With ethylbenzene, on
the other hand, an epoxide intermediate does not appear to be involved in its
major pathway of metabolism (Kiese and Lenk, 1973, 1974; McMahon and Sullivan,
1967, 1968; Sullivan e£ al., 1976; Bakke and Scheline, 1970; Kaubish et_ al_.,
1972).
Administration of styrene, a-methylstyrene, or ethylbenzene to animals
produces a variety of toxic effects which, for the most part, resemble those
seen in humans. Toxicity by acute exposure to these compounds is relatively
low; oral LDsn doses range from three to ten g/kg of body weight in rats and
mice (Wolf eital. , 1956; Spencer ££ al. , 1942; Smyth et^ al., 1962). Differ-
ences in species susceptibility account for wide variability in lethal doses.
With acute exposure to any of these compounds, however, the symptoms are
similar in all species. Both oral administration and inhalation of vapors
result in irritation, incoordination, tremors, convulsions, and other signs
of central nervous system involvement. Ethylbenzene appears to be somewhat
less acutely toxic than styrene.
Repeated feeding or vapor inhalation of styrene, a-methylstyrene, or
ethylbenzene is generally well-tolerated by most mammalian species (Spencer
e_t a_l. , 1942; Wolf et^ a_l. , 1956). With rats exposed to styrene, no histo-
pathologic lesions resulted from repeated feedings of 2000 mg/kg of body
weight (5 days per week for 4 weeks) or from inhalation of vapors at a concen-
tration of 2000 ppm (8 hours per day, 5 days per week for up to 6 months).
However, with ethylbenzene, lesions of the hepatic parenchymal cells and renal
tubular epithelium resulted from doses of 680 mg/kg (oral) and 1250 ppm (in-
halation) using the same treatment schedule. In addition, ethylbenzene at a
231
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concentration of 600 ppm produced a degeneration of the germinal epithelium in
the testes of rabbits and Rhesus monkeys. Although a-methylstyrene produced
no histopathologic changes in rats or guinea pigs inhaling vapors at a con-
centration of 3000 ppm, significant mortality resulted during daily seven-hour
exposures which continued for more than three days.
By virtue of its probable biotransformation to styrene oxide, a possible
carcinogen, styrene has been considered a likely candidate for both mutageni-
city and carcinogeniclty testing. In microbial test systems using various
strains of Salmonella typhimurium, styrene induced reverse mutations (base-
pair substitutions) when incubated in the presence of liver microsomes to
provide metabolic activation (Vainio jet al_., 1976; DeMeester e£ al., 1977).
This mutagenic activity was presumably due to styrene oxide formed metabolically
(Milvy and Garro, 1976). In eukaryotic cells (yeast and hamster) which detect
forward mutations, styrene oxide was a potent direct-acting mutagen, whereas
styrene yielded only equivocal results, even in the presence of liver microsomes
(Loprieno e_t al., 1976; Abbondandolo et al^, 1976). Poor conversion of styrene
to styrene oxide and/or the extremely short half-life of styrene oxide in mammal-
ian cells may account for the lack of an observed mutagenic effect. No informa-
tion is available in the published literature concerning the mutagenicity of tx-
methylstyrene, ethylbenzene, or divinylbenzene.
The positive mutagenicity of styrene in certain test systems has been
taken as presumptive evidence in support of possible carcinogenic activity.
However, the only bioassay conducted for styrene carcinogenicity has yielded
generally unreliable data (Manufacturing Chemists Association, 1978). Never-
theless, female rats inhaling styrene at concentrations of either 600 ppm or
232
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1000 ppm (6 hours per day, 5 days per week for nearly 2 years) displayed an
increase in tumors of lymphatic or hematopoietic origin. Results from other
long-term studies still in progress have not yet become available. Earlier
studies conducted with the presumed styrene metabolite, styrene oxide, indi-
cated an apparent increase in malignant lymphomas among a small group of C3H
mice receiving a total dose of 20 urn styrene oxide by skin painting (Kotin and
Falk, 1963). Furthermore, it has been shown that exposure of cultured C3H
mouse embryo cells to styrene oxide can increase the rate of neoplastic trans-
formation induced by 3-methylcholanthrene (Nesnow and Heidelberger, 1976).
This effect is thought to result either by the inhibition of epoxide hydrase,
an important enzyme for detoxification, or by the depletion of glutathione.
The addition of styrene to the cell culture system had no effect on transfor-
ma t ion, however.
Thus it appears that the potential carcinogenic activity of styrene to a
particular species or individual may well be determined by the steady-state
level of activated metabolite (i.e., styrene oxide) produced in target organ
cells. Moreover, it is not known whether different organs or heterogeneous
cell populations in the same individual may have differing capacities for con-
version of styrene to the epoxide and for the enzymatic detoxification of
potentially carcinogenic metabolites.
Information is not presently available regarding the potential for neo-
plastic transformation in animals or man by direct exposure to ethylbenzene,
divinylbenzene, or a-methylstyrene. However, the fact that ethylbenzene is
apparently not metabolized via an epoxide intermediate suggests that its
activity may differ from that of styrene.
233
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Little is known concerning the effects of styrene, a-methylstyrene,
divinylbenzene, or ethylbenzene on fish, plants, and other lower organisms in
the environment. Both styrene and ethylbenzene are toxic to fish (Fathead,
bluegill, goldfish, guppy), with lethal doses varying with the particular
species employed (Pickering and Henderson, 1966). The 24-hour TLM values
ranged from 35.08 to 97.10 mg/Jl with ethylbenzene and from 25.05 to 74.83 mg/£
with styrene. Neither compound showed any evidence of cumulative toxicity
over time. Styrene and a-methylstyrene are toxic to certain algae and molds,
but concentrations required to produce adverse effects must exceed 0.5%
(Grbid and Munjko, 1977). One author has stated that ethylbenzene inhibits
the growth of heterotrophic bacteria at concentrations exceeding 100 mg/£
(Zubritskii, 1962).
In conclusion, it is apparent that in occupational situations styrene, a-
methylstyrene, and ethylbenzene can elicit toxic responses in workers who are
either acutely or chronically exposed. Among these adverse effects are an
increased incidence of chromosome aberrations and a possible elevation in the
rate of certain malignancies in styrene workers. There is no evidence that
present levels of these chemicals in the non-occupational environment are respon-
sible for, or may contribute to, adverse public health effects. However, since
the potential carcinogenicity of styrene is presently unresolved, a definitive
judgement on its health hazards must await the results of animal bioassays and
more thorough epidemiologic studies. Moreover, the lack of mutagenicity, terato-
genicity, and carcinogenicity data concerning ethylbenzene and a-methylstyrene,
and the total lack of data concerning divinylbenzene toxicity, prevent a reliable
assessment of health and environmental risks. The effect of ethylbenzene on
fertility may be of particular concern in light of its damaging effects on the
testicular germinal epithelium.
234
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TECHNICAL REPORT DATA
(Please rend /uun/criu/u on rlie wciw before completing)
I REPORT NO
EPA 560-11-80-018
3 RECIPIENT'S ACCESSIOI*NO
4 TITLE AND SUBTITLE
Investigation of Selected Potential Environmental
Contaminants: Styrene, Ethylbenzene, and Related
S REPORT DATE
May 1980
6. PERFORMING ORGANIZATION CODE
fomnoiinds
7 AUTHORIS)
J. Santodonato, W.M. Meylan, L.N. Davis, P.H. Howard,
D.M. Orzel, D.A. Bogyo
8 PERFORMING ORGANIZATION REPORT NO
TR 80-569
9 PERFORMING ORGANIZATION NAME AND ADDRESS
Center for Chemical Hazard Assessment
Syracuse Research Corporation
Merrill Lane, University Heights
.Syracuse, New York 13210
10 PROGRAM ELEMENT NO
11 CONTRACT/GRANT NO.
EPA 68-01-3250
12 SPONSORING AGENCY NAME AND. ADDRESS
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, B.C. 20460
13 TYPE OF REPORT AND PERIOD COVERED
Final Technical Report
14. SPONSORING AGENCY CODE
15 SUPPLEMENTARY NOTES
16. ABSTRACT
This report reviews the potential environmental hazard from the commercial
use of four related compounds: ethylbenzene, styrene, a-methylstyrene, and
divinylbenzene. Both ethylbenzene and styrene are produced in 6-7 billion pounds
per year while the other two compounds are produced in much smaller quantities.
Ethylbenzene is used to produce styrene and styrene and the other monomers are
used to make polystyrene and other resins, elastomers, and rubbers. Significant
non-commercial sources of the compounds are also possible including automobile
exhaust, gasolin*>, and other combustion sources. Ethylbenzene and styrene have
both been detected in air and water samples. Information on physical and chemical
properties, production methods and quantities, commercial uses and factors affect-
ing environmental contamination and information related to health and biological
are reviewed.
17
KEY WORDS ANO DOCUMENT ANALYSIS
DESCRIPTORS
styrene
ethylbenzene
a-methylstyrene
divinylbenzene
toxicity
chemistry
b IDENTIFIERS/OPEN ENDED TERMS
r COSATI field/Group
vinylbenzenes
styrenes
8 UliTHIQUTION STATEMENT
Document is available to the public
through the National Technical Informa-
tion Service. Springfield, Va. 22151
19 SECURITY CLASS (Tins Report)
21
NO OF PAf.tb
276
20 SECURITY CLASS (This pa*;eI
22 PRICE
EPA Form 2220-1 (9-73)
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