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

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                                   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

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                      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

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                          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

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                          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

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                           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)

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                            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

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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

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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

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     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

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                   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

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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

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                 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.

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                                      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)

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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

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            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

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                 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

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          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

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           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.

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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

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          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

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                                               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)

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                         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

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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

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         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

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                                                                                             *
        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

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               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

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 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

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         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

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                    (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

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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

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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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•'same site

-------
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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X
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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 .





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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)















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.





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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)
















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.





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-------
            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

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'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

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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

-------
(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

-------
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

-------
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

-------
                  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

-------
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

-------
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

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                  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

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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

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                      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

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                    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

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                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.






                                     131

-------
                    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

-------
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

-------
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

-------
               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

-------
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/&.
                                      136

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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

-------
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

-------
          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

-------
                                           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

-------
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

-------
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

-------
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

-------
                    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

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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

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                     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

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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
                                     211

-------
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%.
                                      212

-------
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


                                     213

-------
               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

-------
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.
                                      215

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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
                                   216

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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).
                                      222

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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
                                     229

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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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Omori, T., Yoshifumi, J., and Minoda, Y. (1974), "Microbial Oxidation of
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Opdyke, D.L.J. (1975), "Monographs on Fragrance Raw Materials -.Ethylbenzene,"
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Pagano, G., Esposito, A., Giordano, G., and Hagstrom, B. (1978), "Embryotoxic
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                                    252

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Pannain, B. and Scala, A. (1960), "Electrophoretic Modifications of Serum
     Proteins, Lipoproteins, and Glycoproteins in Subacute Experimental
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Pantarotto, C., Fanelli, R., Bidoli, F., Morazzoni, P., Salmona, M., and
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Parkes, D.G., Ganz, C.R., Polinsky, A., and Schulze, J. (1976), "A Simple Gas
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Parkki, M.G., Marniemi, J., and Vainio, H. (1976), "Action of Styrene and Its
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Parkki, M.G. (1978), "The role of glutathione in the toxicity of styrene,"
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Paul, S.K. and Soder, S.L.  (1977), "Ethylbenzene - Salient Statistics," Chemical
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Pavlova, L.P. and Agamova, L.P. (1974), "Effect of Low Styrene Concentrations
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Pervier, J.W., Barley, R.C., Field, D.E., Friedman, B.M., and Morris, R.B.
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PfSffli, P., Vainio, H., and Hesso, A. (1979), "Styrene and styrene oxide concen-
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Philippe, R., Lauwerys, R., Buchet, J.P., and Reels, H. (1971), "Evaluation
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Pokrovskii, V.A. and Volchkova, R.I. (1968), "Effect of Some Organic Poisons on
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                                     253

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Ragelis, E.P. and Gajan, R.J. (1962), "Determination of Styrene Monomer in
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Ragule, N. (1974), "Embryotropic Action of Styrene," Gig. Sanit., (ll):85-86.

Ramsey, J.C., and Young, J.D. (1978) "Pharmacokinetics of inhaled styrene in
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Reichel, W.L., Prouty, R.M., and Gay, M.L. (1977), "Identification of Poly-
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Ryan, A., James, M., Ben-Zvi, Z., Law, F., and Bend, J. (1976), "Hepatic and
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                                    257

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                                   261

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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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