United States
Environmental Protection
Agency
Industrial Environmental Research
Laboratory
Cincinnati OH 45268
Research & Development
&EPA Dioxins
600280197
J
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EPA-600/2-80-197
November 1980
DIOXINS
M.P. Esposito, T.O. Tiernan, and
Forrest E. Dryden
Contract Nos. 68-03-2577
68-03-2659
68-03-2579
Project Officer
David R. Watkins
Industrial Pollution Control Division
Industrial Environmental Research Laboratory
Cincinnati, Ohio 45268
U.S. Bnvlponfflental Pr^otiftn
Beft'ion 5, Library (.V.
ESO S. Dearborn Strse
.'. i ,1
loom 1670
diioago, IL 60604
INDUSTRIAL ENVIRONMENTAL RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OHIO 45268
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DISCLAIMER
This report has been reviewed by the Industrial Environmental Research
Laboratory-Cincinnati (lERL-Ci), U.S. Environmental Protection Agency, and
approved for publication. Approval does not signify that the contents necessarily
reflect the views and policies of the U.S. Environmental Protection Agency, nor
does mention of trade names or commercial products constitute endorsement or
recommendation for use.
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FOREWORD
When energy and material resources are extracted, processed, converted, and
used, the related pollutional impacts on our environment and even on our health
often require that new and increasingly more efficient pollution control methods be
used. The Industrial Environmental Research Laboratory-Cincinnati (lERL-Ci)
assists in developing and demonstrating new and improved methodologies that will
meet these needs both efficiently and economically.
This report deals with a group of hazardous chemical compounds known as
dioxins. The extreme toxicity of one of these chemicals, 2,3,7,8-tetrachloro-
dibenzo-p-dioxin (2,3,7,8-TCDD), has been a concern of both scientific
researchers and the public for many years. The sheer mass of published
information that has resulted from this concern has created difficulties in assessing
the overall scope of the dioxin problem. In this report, the voluminous data on
2,3,7,8-TCDD and other dioxins are summarized and assembled in a manner that
allows comparison of related observations from many sources; thus, the report
serves as a comprehensive guide in evaluation of the environmental hazards of
dioxins.
Sections 2 and 3 present detailed information on the chemistry and sources of
dioxins. Various routes of formation of dioxins are discussed, and the possible
presence of dioxins in basic organic chemicals and pesticides is addressed. Section 4
details the development of an analytical method for detecting part-per-trillion
levels of dioxins in industrial wastes. Sections 5 through 8 discuss routes of human
exposure to dioxins, including accounts of public and occupational exposure, and
the health effects, environmental degradation, transport, and disposal of dioxins.
David G. Stephan
Director
Industrial Environmental Research Laboratory
Cincinnati
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PREFACE
This report deals with a group of hazardous chemical compounds known as
dioxins. The report discusses the detailed chemistry of dioxin formation and
identifies types of organic chemicals and pesticides which may have dioxins
associated with them as impurities or byproducts. It investigates the development
of an analytical technique for identifying dioxins in industrial wastes. Finally, it
summarizes the reported incidents of human exposure to dioxins, and examines
the toxicity, environmental transport, and techniques available for
decontamination and disposal of dioxin-contaminated material.
An extensive amount of literature published during the past 25 years has been
concerned primarily with one extremely toxic member of this class of compounds,
2,3,7,8-tetrachlorodibenzo-p-dioxin. Often described in both popular and
technical literature as "TCDD" or simply "dioxin," this compound is one of the
most toxic substances known to science. This report, however, is concerned not
only with this compound, but also with all of its chemical relatives that contain the
dioxin nucleus. Throughout this report, the term "TCDD's" is used to indicate the
family of 22 tetrachlorodibenzo-p-dioxin isomers, whereas the term "dioxin" is
used to indicate any compound with the basic dioxin nucleus. The most toxic
isomer among those that have been assessed is specifically designated as
"2,3,7,8-TCDD."
The objective in the use of these terms is to clarify a point of technical confusion
that has occasionally hindered comparison of information from various sources. In
particular, early laboratory analyses often reported the presence of "TCDD,"
which may have been the most-toxic 2,3,7,8-isomer or may have been a mixture of
several of the tetrachloro isomers, some of which are relatively nontoxic.
Throughout this report, the specific term 2,3,7,8-TCDD is used when it was the
intent of the investigator to refer to this most-toxic isomer. Since early analytical
methods could not dependably isolate specific isomers from environmental
samples, the generic term "TCDD's" is used when this term appears to be most
appropriate in light of present technology.
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ABSTRACT
Concern about the potential contamination of the environment by dibenzo-p-
dioxins through the use of certain chemicals and disposal of associated wastes
prompted this study.
This report reviews the extensive amount of dioxin literature that has become
available in recent years. Although most published reports deal exclusively with the
highly toxic dioxin 2,3,7,8-TCDD, some include information on other dioxins.
These latter reports were sought out so that a document covering dioxins as a class
of chemical compounds could be prepared.
A brief description of what is known about the chemistry of dioxins is presented
first. Chemical reaction mechanisms by which dioxins may be formed are reviewed,
particularly those likely to occur within commercially significant processes.
Various routes of formation are identified in addition to the classical route of the
hydrolysis of trichlorophenol. Basic organic chemicals and pesticides with a
reasonable potential for dioxin byproduct contamination are surveyed as to
current and past producers and production locations. Classifications are presented
both for general organic chemicals and for pesticides that indicate likelihood of
dioxin formation. Conditions are noted that are most likely to promote dioxin
formation in various processes.
An analytical approach for use in quantifying part-per-trillion levels of TCDD's
in various chemical wastes is included in this report. The Brehm Laboratory of
Wright State University examined waste samples provided by the Environmental
Protection Agency from plants manufacturing trichlorophenol,
pentachlorophenol, and hexachlorophene, and from plants processing wood
preservatives. The extraction procedure developed for isolating TCDD's from
the various types of sample matrices is fully described. The analysis using highly
specific and sensitive coupled gas chromatographic-mass spectrometric (GC-MS)
methods is also described in detail. TCDD's were detected and quantitatively
determined in several of the samples at levels in the ppt to ppm range.
Incidents of human exposure to dioxins are reviewed and summarized. A review
of the known health effects of 2,3,7,8-TCDD and other dioxins is presented. Many
toxicological studies of the effects produced by chronic exposures to these
toxicants and the possible mechanisms of action are described.
Reports on possible routes of degradation are characterized. Finally, current
methods of disposal of dioxin-contaminated materials are described, and possible
advanced techniques for ultimate disposal are outlined.
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CONTENTS
Foreword iii
Preface iv
Abstract v
List of Figures vjjj
List of Tables xii
Acknowledgements xv
List of Abbreviations xvi
1. Introduction 1
2. Formation of Dibenzo-p-Dioxins 3
3. Sources of Dioxins 37
4. Analytical Method for Dioxins in Industrial Wastes 133
5. Routes of Human Exposures 168
6. Health Effects 187
7. Environmental Degradation and Transport 230
8. Disposal and Decontamination 257
References 271
Appendix A 307
Appendix B 344
Index 348
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LIST OF FIGURES
Figure 1. Formation of Dioxins 7
Figure 2. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 4-Bromo-2,5-Dichlorophenol 44
Figure 3. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2-Chloro-4-fluorophenol 45
Figure 4. Proposed Reaction Mechanism for Dioxin Formation
in the Production of Decabromophenoxybenzene 46
Figure 5. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,4-Dibromophenol 47
Figure 6. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,3-Dichlorophenol 48
Figure 7. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,4-Dichlorophenol 49
Figure 8. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,5-Dichlorophenol 50
Figure 9. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,6-Dichlorophenol 51
Figure 10. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 3,4-Dichlorophenol 52
Figure 11. Proposed Reaction Mechanism for Dioxin Formation
in the Production of Pentabromophenol 53
Figure 12. Proposed Reaction Mechanism for Dioxin Formation
in the Production of 2,4,6-Tribromophenol 54
Figure 13. 2,4,5-Trichlorophenol, 2,4,5-T and Esters and Salts 59
Figure 14. Silvex and Esters and Salts 60
Figure 15. Ronnel 61
Figure 16. Erbon and Sesone 62
Figure 17. 2,4-D and Esters and Salts 64
Figure 18. 2,4-DB 65
Figure 19. 2,4-D P 66
(continued)
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LIST OF FIGURES (continued)
Figure 20. Dicapthon and Dichlofenthion 67
Figure 21. Bifenox 68
Figure 22. Nitrofen 69
Figure 23. Dicamba , 70
Figure 24 Pentachlorophenol (PCP) Via Phenol 71
Figure 25. Pentachlorophenol (PCP) Via Hexachlorobenzene 72
Figure 26. Chloranil 73
Figure 27. Hexachlorophene and Isobac 20 74
Figure 28. 2,3,4,6-Tetrachlorophenol 75
Figure 29. Basic Chlorophenol Reactions 84
Figure 30. Direct Chlorination of Phenol 86
Figure 31. Flow Chart for 2,4,5-TCP Manufacture 91
Figure 32 Flow Chart for Hexachlorophene Manufacture 108
Figure 33. Locations of Current and Former Producers
of Chlorophenols and Their Derivatives 114
Figure 34. Apparatus for Gas Chromatography 135
Figure 35. Schematic Diagram of a Nier 60° Sector Mass Spectrometer 136
Figure 36. Electron-Impact Ion Source and Ion Accelerating System 137
Figure 37. Mass Chromatogram of Extract of Sample 2, at m/e 322
Obtained with GC-QMS 147
Figure 38. High Pressure Liquid Chromatogram of Sample 2 152
Figure 39. High Pressure Liquid Chromatogram of 2,3,7,8-TCDD
Standard 153
Figure 40. Four-Ion Mass Fragmentogram of Benzene Solvent Blank
Obtained with GC-MS-30 155
Figure 41. Four-Ion Mass Fragmentogram of 50 pg 2,3,7,8-TCDD and
1 ng "Cl4-2,3,7,8-TCDD Obtained with GC-MS-30 155
Figure 42. Four-Ion Mass Fragmentogram of Sample 12700 Obtained
with GC-MS-30 156
Figure 43. Four-Ion Mass Fragmentogram of Sample 5 Obtained with
GC-MS-30 157
(continued)
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LIST OF FIGURES (continued)
Figure 44. Dual-Ion Mass Fragmentogram of Sample 2 Obtained with
GC-MS-30, Mass Resolution 1:12,500 161
Figure 45. Dual-Ion Mass Fragmentogram of 150 pg of 2,3,7,8-TCDD
Standard Obtained with GC-MS-30, Mass Resolution
1:12,500 162
Figure 46. Mass Fragmentograms Using GC-MS-30 of Mixtures
of 2,3,7,8-TCDD with Other Chlorinated Compounds 163
Figure 47. Mass Spectra from Scans of 2,3,7,8-TCDD Standard
and Sample 2 165
Figure 48. Mass Spectra from Scans of 2,3,7,8-TCDD Standard
and Sample 2 166
Figure 49. Map of Seveso Area Showing Zones of Contamination
(A and B) and Zone of Respect (R) 169
Figure 50. Excretion of 14C Activity by Rats Following a Single Oral
Dose of 50 Mg/kg (0.14 jiCi/kg) 2,3,7,8-TCDD 192
Figure 51. Proposed Mechanism for Induction of AHH and Toxicity
by 2,3,7,8-TCDD 194
Figure 52. Schematic of Rat Liver 13 Days After Administration
of 2,3,7,8-TCDD (50 ng/ kg) 196
Figure 53. Drawing of Tissue from Heart of Monkey Fed 2,3,7,8-TCDD 198
Figure 54. Drawing of Heart Tissue from Monkey fed 2,3,7,8-TCDD 199
Figure 55. Drawing of Section of Skin of Monkey Fed 2,3,7,8-TCDD 200
Figure 56. Drawing of Part of a Multinucleated Liver Cell from a
Female Rat Given 0.1 Mg of 2,3,7,8-TCDD/kg/day
for 2 Years 201
Figure 57. Drawing of Liver Tissue from Rat Fed 2,3,7,8-TCDD 202
Figure 58. Drawing of Normal Membrane Junctions from the
Periportal Region of a Test Animal 42 Days After
Administration of 200 fig/ kg 2,3,7,8-TCDD 203
Figure 59. Drawing of Distorted Periportal Membrane Junction;
Showing Loss of Continuity of Plasma Membranes
Between Parenchyma! Cells 204
Figure 60. Focal Alveolar Hyperplasia Near Terminal Bronchiole
within Lung of Rat Given 2,3,7,8-TCDD at Dosage
of 0.1 figj kg Per Day 205
Figure 61. Lesion Classified Morphologically as Hepatocellular
Carcinoma in Liver of Rat Given 0.1 fig of 2,3,7,8-TCDD/
kg per Day 218
(continued)
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LIST OF FIGURES (continued)
Figure 62. Lesion within Lung of Rat Given 0.1 Mg of 2,3,7,8-TCDD/
kg per Day 219
Figure 63. Linear Correlation of New South Wales Rate for Neural-
Tube Defects with Previous Year's Usage of 2,3,7,8-TCDD
in Australia 228
Figure 64. Map of Test Area C-52A, Eglin Air Force Base Reservation,
Florida , 242
Figure 65. Diagram of Microagroecosystem Chamber 245
Figure 66. Location of Farms near Seveso at Which Cow's Milk
Samples Were Collected for TCDD Analysis in 1976
(July-August) 252
Figure 67. Schematic of Molten-Salt Combustion Process 261
Figure 68. Schematic of Microwave Plasma System 262
Figure 69. Schematic for Ozonation/Ultraviolet Irradiation Apparatus 265
Figure 70. Internal View of Pesticide Micropit 270
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LIST OF TABLES
Table 1. Chlorinated Dioxins 4
Table 2. Physical Properties of Two Chlorinated Dioxins 5
Table 3. Perhalo Dibenzo-p-Dioxins Via Free Radical Reactions 14
Table 4. Ullmann Condensation Reactions 16
Table 5. Catechol-Based Reactions 27
Table 6. Substitution Reactions 30
Table 7. Organic Chemicals Related to Dioxin Formation 38
Table 8. List of Pesticide Chemicals 55
Table 9. Higher Chlorinated Dioxins Found in Commercial
Pesticides 58
Table 10. Pesticide Raw Materials 76
Table 11. Chlorodioxins Reported in Chlorophenols 79
Table 12. Commercial Chlorophenols and Their Producers 83
Table 13. 1977 Pentachlorophenol Production Capacity 88
Table 14. Former 2,4,5-TCP Manufacturing Sites 93
Table 15. Current Basic Producers of 2,4-D and 2,4-DB Acids, Esters,
and Salts 96
Table 16. Former Basic Producers of 2,4-D and 2,4-DB Acids, Esters,
and Salts 97
Table 17. Derivatives of 2,4,5-Trichlorophenol and Their Recent
(1978) Producers 100
Table 18. Former Producers of 2,4,5-T (Prior to 1978) 101
Table 19. Locations of Current and Former Producers of
Chlorophenols and Their Derivatives 115
Table 20. Dioxins in Selected Samples 126
Table 21. Sources of Purified Dioxin Samples for Research 130
Table 22. Samples Used in Development of Analytical Method for
TCDD's in Industrial Wastes 145
(continued)
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LIST OF TABLES (continued)
Table 23. Elution of TCDD's in Extracts of Sample 2 148
Table 24. Content of TCDD's in Column Fraction for Sample 2 149
Table 25. Recovery of 2,3,7,8-TCDD Spike from Eluates of
Sample CO4131 150
Table 26. Results of GC-MS-30 Analysis of EPA Samples for TCDD's 154
Table 27. TCDD Isomer Content of Column Fraction Samples Spiked
with 2,3,7,8-TCDD 159
Table 28. Recoveries of 2,3,7,8-TCDD-Spiked Samples Following
Alumina Column Chromatography 160
Table 29. Results of GC-MS-30 Analysis of Samples Spiked with
37Cl4-2,3,7,8-TCDD 160
Table 30. Relative Intensities of Major Ions Observed in Mass
Spectral Scans 164
Table 31. Dioxins in Commercial Gelatin 176
Table 32. Reported Incidents of Occupational Exposure to Dioxins
During Routine Chemical Manufacturing 181
Table 33. Occupational Exposure to Dioxins Through Accidents
in the Chemical Manufacturing Industry 182
Table 34. Industries Using Dioxin-Related Chemicals 184
Table 35. Toxicities of Selected Poisons 188
Table 36. Biological Properties of Dioxins 189
Table 37. Enzyme Induction 190
Table 38. 14C Body Burden Activity in Six Rats Given a Single Oral
Dose of 1.0 yug of 14C-2,3,7,8-TCDD/kg 191
Table 39. Toxicities of Organic Pesticides and 2,3,7,8-TCDD 206
Table 40. Acute Toxicities of Dioxins 207
Table 41. Acute Toxicities of 2,3,7,8-TCDD for Various Species 207
Table 42. Summary of Acute Toxicity Effects of 2,3,7,8-TCDD 208
Table 43. Effects of In Vivo 2,3,7,8-TCDD Exposure on Functional
Immunological Parameters 212
Table 44. Summary of Neoplastic Alterations Observed in Rats Fed
Subacute Levels of 2,3,7,8-TCDD for 78 Weeks 217
Table 45. Mutagenicity of Dioxin Compounds in
Salmonella Typhimurium 220
(continued)
Xlll
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LIST OF TABLES (continued)
Table 46. Combined Rate of Neural-Tube Defects in
New South Wales and Previous-Year Usage of 2,4,5-T
in Australia 227
Table 47. Concentrations of Herbicide Orange and 2,3,7,8-TCDD in
Three Treated Test Plots 232
Table 48. Degradation of 2,3,7,8-TCDD in Soil 233
Table 49. Photodegradation of 2,3,7,8-TCDD 235
Table 50. Photodegradation of DCDD and OCDD 238
Table 51. Concentrations of 2,3,7,8-TCDD at Utah Test Range
4 Years After Herbicide Orange Applications 244
Table 52. Concentrations of 2,3,7,8-TCDD at Eglin Air Force Base
414 Days After Herbicide Orange Application 244
Table 53. TCDD Levels in Wildlife 248
Table 54. TCDD Levels in Milk Samples Collected near Seveso in
July-August 1976 251
Table 55. Soil Application Rates and Replications
254
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ACKNOWLEDGMENTS
The material in this report was prepared by three contractors: PEDCo
Environmental, Inc., the Brehm Laboratory and Chemistry Department of Wright
State University, and Walk, Haydel & Associates, Inc. Final compilation of the
material was done by PEDCo Environmental, Inc.
Richard W. Gerstle directed the project at PEDCo, with Ms. M. Pat Esposito as
Project Manager and principal investigator. Others contributing to the work
included Mr. H. M. Drake, Dr. Jeffrey A. Smith, Mr. Timothy W. Owens,
Ms. Diane N. Albrinck, Dr. Terrence W. Briggs, Mr. A. Christian Worrell, and
Ms. Lauren J. Smith of PEDCo; and Dr. F. Howard Schneider, of Bioassay
Systems Corporation.
Dr. T. O. Tiernan was the principle investigator at Wright State University, with
Dr. M. L. Taylor and Dr. S. D. Erk as co-principle investigators. Others
contributing to the work included Mr. J. G. Solch, Mr. G. Van Ness, and
Mr. J. Dryden.
Mr. Forrest E. Dryden directed, managed, and contributed to the preparation of
the report at Walk, Haydel & Associates. Others contributing to the work included
Mr. Harry E. Ensley, Mr. Ronald J. Rossi, Mr. E. Jasper Westbrook,
Mr. Robert J. Planchet, Mr. Jerome F. Pankow, and Mr. William J. Kimsey, Jr.
The cooperation of the many organizations and individuals who assisted in the
collection of this material is appreciated. Special thanks go to Dr. Warren
Crummett of Dow Chemical Company, Dr. S. Garattini of Maria Negri Institute,
Italy, Dr. G. Reggiani of Hoffman-LaRoche, Switzerland, and Dr. Pat Sferra of
U.S. EPA, lERL-Cincinnati, for reviewing the document and providing helpful
and clarifying points of information. In addition, we would like to acknowledge
Battelle Columbus Laboratories, Columbus, Ohio, for their part in the evaluation
of disposal and decontamination technology, and for the review of the analytical
literature of TCDD's in various sample matrices. We also thank Mary Reece and
Harvey Warnick (Office of Pesticide Programs, EPA), Charles Auer (Office of
Toxic Substances, EPA), and Captain Alvin Young (U.S. Air Force) for their
technical assistance.
The chemical figures used throughout this report were provided by Walk,
Haydel & Associates, and all final editorial and production work was handled by
WAPORA, Inc.
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LIST OF ABBREVIATIONS
cm centimeter
DBDCDD's dibromodichlorodibenzo-p-dioxins
DBDD's dibromodibenzo-/?-dioxins
DCDD's dichlorodibenzo-p-dioxins
DDE 2,2-bis-(p-chlorophenyl)-1,1 -dichloroethylene
dioxins dibenzo-p-dioxins
DFDD's difluorodibenzo-p-dioxins
DM SO dimethyl sulfoxide
DNDD's dinitrodibenzo-p-dioxins
eV electron volt
g gram
GC gas chromatography
GC-EC gas chromatography-electron capture
GC-MS gas chromatography-mass spectrometry
GC-MS-30 gas chromatography-mass spectrometry (high resolution)
GC-QMS gas chromatography-quadrupole mass spectrometry
(low resolution)
Hexa-CDD's hexachlorodibenzo-p-dioxins
Hepta-CDD's heptachlorodibenzo-/?-dioxins
HPLC high-pressure liquid chromatography
I.D. inside diameter
kg kilogram
LDjo lethal dose to 50% of test group
m meter
MCDD's monochlorodibenzo-p-dioxins
m/e mass to charge ratio
ml milliliter
ml / min milliliter / minute
mm millimeter
MS mass spectrometry
ng nanogram
OBDD octabromodibenzo-p-dioxin
OCDD octachlorodibenzo-p-dioxin
PCB polychlorinated biphenyl
PCP pentachlorophenol
Penta-CDD's pentachlorodibenzo-/?-dioxins
(continued)
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LIST OF ABBREVIATIONS (continued)
pg picogram
ppb parts per billion (/ug/1 or ng/ml)
ppm parts per million (mg/1 or /ug/ml)
ppt parts per trillion (ng/1 or pg/ml)
psig pounds per square inch gage
TBDD's tetrabromodibenzo-p-dioxins
TCDD's tetrachlorodibenzo-p-dioxins
TCP trichlorophehol
Tri-CDD's trichlorodibenzo-p-dioxins
2,3,7,8-TCDD 2,3,7,8-tetrachlorodibenzo-/?-dioxin.
2,4,5-TCP 2,4,5-trichlorophenol
/ug microgram
UV ultraviolet
V volt
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SECTION 1
INTRODUCTION
The growing concern with contamination of the environment by dioxins arises
principally from their potential toxicity and their distribution as contaminants in
commercial products. The purpose of this report is to present in a systematic and
summary manner what is currently known about dioxins and their effects.
Although most published reports deal exclusively with the highly toxic dioxin 2,3,
7, 8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), some include information on
other dioxins. These latter reports were sought out so that a document covering
dioxins as a class of chemical compounds could be prepared.
Although 2,3,7,8-TCDD was first reported in the chemical literature in 1872, no
major investigations into its toxicity were begun until the 1950's. Because of the
remarkable stability of this substance in biological systems and its extreme toxicity,
cumulative effects of extremely small doses are a major concern. For example, the
LDJO of 2,3,7,8-TCDD for the male guinea pig has been shown to be only 0.6
jj. g/kg orO. 6 part per billion body weight (McConnelletal. 1978). Fetal mortality
has been observed in rats that had been fed 10 consecutive doses of 2,3,7,8-TCDD
at the level of 0.125 p g/kg per day (World Health Organization 1977). It is
reasonable to presume, therefore, that the slightest trace of 2,3,7,8-TCDD in the
environment may have adverse effects on the health of both human and animal
populations.
In view of these considerations, it is vitally important to scrutinize carefully the
probable avenues of contamination of the environment with 2,3,7,8-TCDD. It has
been recognized for some time that 2,3,7,8-TCDD can be produced in the
manufacture of 2,4,5-trichlorophenol. Other dioxins are similarly produced in the
manufacture of other chlorophenols. The amounts of dioxins produced depend on
process controls such as temperature and pressure. Since dioxins may be present in
these and other manufactured chemical products, it is also likely that they may be
present in the chemical wastes and sludges remaining from these processes. If this is
the case, indiscriminate discharge of these wastes into the environment, or the use
of improper disposal procedures could lead to the contamination of water, air, or
foodstuffs. This might, in turn, result in widespread exposure of the population to
TCDD's and other dioxins.
The report first presents an account of the chemistry of dioxins (Section 2), their
physical and chemical properties and modes of formation. Section 3 considers the
sources of dioxins, focusing on basic organic chemicals as well as on the chemical
manufacture of chlorinated phenols and their derivatives.
Section 4 discusses the development of an analytical method for detecting
dioxins in industrial wastes.
Section 5 provides a brief account of the major known incidents of human
exposure to dioxins in the environment. In the aftermath of these incidents, which
include both occupational exposures and exposures of the general public, scientists
of many disciplines have undertaken extensive and continuing investigations of the
fate of dioxins when they are released to the environment.
Section 6 reviews the current scientific knowledge of the health effects of dioxins,
as indicated in epidemiological and laboratory studies of animal and human
subjects who have been exposed to dioxin contamination. Section 7 reviews the
known mechanisms of biodegradation, photodegradation, physical transport, and
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biological transport. The investigations indicate that the persistence of dioxins
poses a serious environmental problem. In attempts to deal with this problem,
numerous environmental research and development projects are aimed at
developing methods of destroying these toxic contaminants after they have been
formed. This work on dioxin disposal methods and decontamination procedures is
described in Section 8.
It is intended that this review of dioxin contaminants, from their formation
through their dispersal into various environmental media and the consequent
effects, can provide a point of perspective for those who are concerned with
regulatory efforts and with research and development directed toward reducing the
hazards of dioxin contamination.
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SECTION 2
FORMATION OF DIBENZO-P-DIOXINS
CHEMISTRY OF DIOXIN FORMATION
A dioxin is any of a family of compounds known chemically as dibenzo-
p-dioxins. Each of these compounds has as a nucleus a triple-ring structure
consisting of two benzene rings interconnected to each other through a pair of
oxygen atoms. Shown below are the structural formula of the dioxin nucleus and
also the abbreviated structural convention used throughout the report.
Each of these substituent positions, numbered 1 through 4 and 6 through 9, can
hold a chlorine or other halogen atom, an organic radical, or (if no other
substituent is indicated in the formula or its chemical name) a hydrogen atom. The
only differences in members of the dioxin family are in the nature and position of
substituents.
Most environmental interest in dioxins and most studies of this family of
compounds have centered on chlorinated dioxins, in which the chlorine atom
occupies one or more of the eight positions. Theoretically, there are 75 different
chlorinated dioxins, each with different physical and chemical properties, differing
only in the number of chlorine atoms in each molecule and in their relative
locations on the dioxin nucleus. There are, for example, two monochlorodioxins,
in which one chlorine atom is attached to the nucleus at either position 1 or position
2. If two or more chlorine atoms are present, additional isomeric forms are
possible, in accordance with the following schedule (Buser, Bosshardt, and Rappe
1978):
2 isomers of monochlorodibenzo-p-dioxin (MCDD's)
10 isomers of dichlorodibenzo-/>dioxin (DCDD's)
14 isomers of trichlorodibenzo-p-dioxin (Tri-CDD's)
22 isomers of tetrachlorodibenzo-p-dioxin (TCDD's)
14 isomers of pentachlorodibenzo-p-dioxin (Penta-CDD's)
10 isomers of hexachlorodibenzo-p-dioxin (Hexa-CDD's)
2 isomers of heptachlorodibenzo-p-dioxin (Hepta-CDD's)
1 octachlorodibenzo-p-dioxin (OCDD)
-------
Table 1 lists the 75 possible chlorinated dioxins, and also notes the 40 that have
been prepared and identified and whose analytical characteristics have been
published (Busep, Bosshardt, and Rappe 1978; Buser 1975; Pohland and Yang
1972; Bolton 1978). Five others, as noted in the table, have been identified as
distinct compounds but have not been clearly differentiated from each other
(Buser, Bosshardt, and Rappe 1978; Buser 1975; Rappe 1978).
TABLET. CHLORINATED DIOXINS
1-chloro
2-chloro
1,2-dichloro
1,3-dichloro
1,4-dichloro
1,6-dichloro
1 ,7-dichloro
1,8-dichloro
1,9-dichloro
2,3-dichloro
2,7-dichloro
2,8-dichloro
1,2,3-trichloro
1,2,4-trichloro
1,2,6-trichloro
1,2,7-trichloro
1,2,8-tnchloro
1,2,9-tnchloro
1,3,6-tnchloro
1,3,7-trichloro
1,3,8-trichloro
1,3,9-tnchloro
1,4,6-trichloro
1,4,7-trichloro
2,3,6-tnchloro
2,3,7-tnchloro
a
a
a
a
a
a
a
a
a
a
a
a
a
1,2,3,4-tetrachloro
1,2,3,6-tetrachloro
1,2,3,7-tetrachloro
1,2,3,8-tetrachloro
1,2,3,9-tetrachloro
1,2,4,6-tetrachloro
1 ,2,4,7-tetrachloro
1,2,4,8-tetrachloro
1,2,4,9-tetrachloro
1,2,6,7-tetrachloro
1,2,6,8-tetrachloro
1,2,6,9-tetrachloro
1,2,7,8-tetrachloro
1,2,7,9-tetrachloro
1,2,8,9-tetrachloro
1,3,6,8-tetrachloro
1,3,6,9-tetrachloro
1,3,7,8-tetrachloro
1,3,7,9-tetrachloro
1,4,6,9-tetrachloro
1,4,7,8-tetrachloro
2,3,7,8-tetrachloro
a,d 1,2,3,4,6-pentachloro
1 ,2,3,4,7-pentachloro
1 , 2,3,6, 7-pentachloro
a 1, 2,3,6, 8-pentachloro
1 ,2,3,6,9-pentachloro
1 ,2, 3,7, 8-pentachloro
1,2,3,7,9-pentachloro
1,2,3,8,9-pentachloro
1,2,4,6,7-pentachloro
a 1 ,2,4,6,8-pentachloro
1,2,4,6,9-pentachloro
a 1,2,4,7. 8-pentachloro
a 1,2,4,7,9-pentachloro
1 , 2,4,8, 9-pentachloro
a 1, 2,3,4, 6,7-hexachloro
a 1, 2,3,4,6, 8-hexachloro
a 1,2,3,4,6,9-hexachloro
a 1 ,2,3,4,7,8-hexachloro
a 1,2,3,6,7,8-hexachloro
a 1,2,3,6,7,9-hexachloro
1 , 2,3,6, 8,9-hexachloro
a 1,2,3, 7, 8,9-hexachloro
1 ,2,4,6,7,9-hexachloro
1,2,4,6,8,9-hexachloro
1 ,2, 3,4,6,7, 8-heptachloro
1 ,2,3,4,6, 7, 9-heptachloro
Octachloro
a
a
c
a
c
a
c
a
a
a
a
a
a
b
a
a
b
a
a
a
a—Identified compounds.
b—One or the other of these compounds has been prepared
c—A mixture of these three compounds has been prepared
d—The Dow Chemical Company has recently reported the synthesis
of all 22 TCDD isomers
The interest of health and environmental researchers in dioxins arose principally
because of the toxicity and distribution of one of these compounds, 2,3,7,8-TCDD,
whose structural formula is as follows:
-------
This is an unusual organic chemical, symmetrical across both horizontal and
vertical axes. It is remarkable for its lack of reactive functional groups and its
chemical stability (Poland and Kende 1976). It is an extremely lipophylic molecule,
and only sparingly soluble in water and most organic liquids; it is a colorless
crystalline solid at room temperature. The physical properties of 2,3,7,8-TCDD are
shown in Table 2, along with those of OCDD, another chlorinated dioxin with
twofold symmetry (World Health Organization 1977; Crummettand Stehl 1973).
TABLE 2. PHYSICAL PROPERTIES OF TWO CHLORINATED DIOXINS
Empiric formula
Percent by weight C
0
H
Cl
Molecular weight
Melting point, °C
Decomposition temperature, °C
Solubilities, g/hter
o-Dichlorobenzene
Chlorobenzene
Anisole
Xylene
Benzene
Chloroform
A?-Octanol
Methanol
Acetone
Dioxane
Water
2.3,7,8-TCDD
C,2H4CI402
44.7
9.95
1 25
44.1
322
305
Above 700
1 4
0.72
0.57
0.37
0048
0.01
0.11
0.0000002 (0 2 ppb)
OCDD
C,2CI802
31.3
7.0
61.7
459 8
130
Above 700
1 83
1.73
358
0.56
0.38
Dioxin Formation from Precursors
No published reports indicate that dioxins are formed biosynthetically by living
organisms; these compounds apparently are not constituents of a normal growing
environment. The presence of dioxins in fly ash, 2-chlorophenol,
2,4,6-trichlorophenol, and hexachlorobenzene indicates that there may be yet-
undiscovered mechanisms that produce these compounds. In a recent study,
chlorinated dioxins were created by pyrolysis of chlorobenzenes in the presence of
air (Buser 1979b). Dioxins have been made from catechols in condensations with
polychlorobenzenes and chloronitrobenzenes (World Health Organization 1977;
Gray et al. 1976; March 1968). A pesticide manufacturer has reported the finding of
chlorinated dioxins in cigarette smoke and fireplace soot (Dow Chemical
Company 1978). Other possible routes of formation are examined in Section 3 of
-------
this report. One route that has been demonstrated by extensive chemical research is
the formation of chlorinated dioxins from industrial chemicals, especially from
certain "precursor" compounds that lead directly to dioxin formation. In
generalized form, this reaction is as follows:
This reaction indicates that a compound may be a dioxin precursor if it meets two
conditions:
• The precursor compound must by an ortho-substituted benzene ring in which
one of the substituents includes an oxygen atom directly attached to the ring.
• It must be possible for the two substituents, excluding the oxygen atom, to
react with each other to form an independent compound.
These conditions are met by many organic compounds, including a class of
mass-produced chemicals, the ortho-chlorinated phenols. The hydroxyl group of
the phenol supplies the ring-attached oxygen atom. The hydrogen of the hydroxyl
group is capable of reacting with chlorine, the other substituent, to form hydrogen
chloride, an independent compound. An even more likely precursor is the sodium
or potassium salt of an ortho-chlorinated phenol because the coproduct of this
condensation is sodium or potassium chloride, either of which is an even more
stable inorganic salt.
Almost all original dioxin researchers used ortho-chlorinated phenols as
precursors. Most often, the reactions were conducted in the presence of sodium or
potassium hydroxide, either of which will react spontaneously with the phenol
groups to form the phenylate salts. Six chemical reactions, all of which have been
performed in laboratory experiments, are shown in Figure 1 (Pohland and Yang
1972; World Health Organization 1977; Crosby, Moilanen, and Wong 1973;
Milnes 1971).
Not all of these reactions, however, have produced the expected dioxin in high
yield, and investigators have detected other dioxins and similar compounds that
were not attributable to these simple reactions. Numerous studies have therefore
explored the reaction mechanism of dioxin formation and the complex of
competing reactions that create other compounds of this type (Buser 1975; Nilsson
?t al. 1974; Jensen and Renberg 1972; Plimmer 1973; Buser 1978).
The basic dioxin reaction actually occurs in two steps. In the condensation of
2,4,5-trichlorophenol, for example, one pair of substituents reacts first to form a
phenoxyphenate, or substituted diphenyl ether, in accordance with the following
reaction (Nilsson et al. 1974; Jensen and Renberg 1972; Buser 1978; Moore 1979).
NaCI
, , ^x^k_.
Cl ONa
PREDIOXIN
Compounds of this type have been termed "predioxins."They have been identified
in waste sludges and commercial products as well as in the products of laboratory
experiments (Jensen and Renberg 1972; Arsenault 1976; Jensen and Renberg
1973).
-------
o-CHLOROPHENOL POTASSIUM SALT
COPPER POWDER
CATALYST
IN WATER AND
POTASSIUM HYDROXIDE
COPPER POWDER
CATALYST^
IN VACUUM _,
SUBLIMATOR Cl
2,4-DICHLOROPHENOL POTASSIUM SALT
Cl
^ONa
CK^^^CI
2,4,6-TRICHLOROPHENOL SODIUM SALT
2,4,5-TRICHLOROPHENOL SODIUM SALT
Cl
CK ^^ ^OK
UNSUBSTITUTED DIOXIN
CONDITIONS
UNREPORTED
VARIETY OF
CONDITIONS
COPPER POWDER
CATALYST
IN VACUUM
SUBLIMATOR Cl
2,3,5,6-TETRACHLOHOPHENOL POTASSIUM SALT
HEATING ONLY
Cl
PENTACHLOROPHENOL
Cl Cl
1,2,4.8,7,9-HEXA-CDD
Figure 1. Formation of dioxins.
There are other competing reactions, however. With some precursor
compounds, condensation may occur with a chlorine atom that is not in the ortho
position to a hydroxyl group. One study suggests that a meta chlorine will be
favored, in accordance with the following reaction (Langer, Brady, and Briggs
1973).
-------
Cl Cl
ISOPREDIOXIN
ONa
Cl
The end product has been termed an "isopredioxin"(Jensenand Renberg 1973).
To this isopredioxin, additional molecules of sodium-2,4,5-trichlorophenate may
attach, creating a polymerized compound of three, four, or more monomers
(Langer, Brady, and Briggs 1973; Langer et al. 1973).
Cl
ONa
Investigators have noted similar reactions with para chlorine atoms, which form
another type of isopredioxin. Either of the isopredioxins may polymerize into
longer chains, or they may lead with loss of chlorine to the creation of
dibenzofurans (Jensen and Renberg 1972; Langer, Brady, and Briggs 1973;
Deinzer et al. 1979; Chemical Engineering 1978).
It is believed that dibenzofurans are also formed by reaction between a
chlorophenol and a polychlorobenzene through an intermediate creation of
another type of diphenyl ether (Buser 1978).
NaOH
Cl
NaCI +
NaCI + H2O
Cl
Another competing reaction that involves loss of chlorine is the reaction to form
dihydroxy chlorinated biphenyls (Jensen and Renberg 1973).
-------
CI2
The chlorine thus released may react with other rings to form compounds with
higher chlorine saturation. Preparation of 2,3,7,8-TCDD was accomplished by
treatment of unsubstituted dioxin (World Health Organization 1977).
Other competing reactions have been described for pentachlorophenol, which
has been shown to degenerate, when heated, into hexachlorobenzene and water by
a reaction sequence that includes an intermediate decachlorodiphenylether
(Plimmer 1973).
Cl
+ HCI
HCI
Cl
Alternatively, the predioxin or the decachlorodiphenylether may lose chlorine
through reactions with water to form hexachloro or heptachlorodioxins or to form
octa- and nonachlorodiphenylethers. Loss of chlorine may also create
octachlorodibenzofuran in accordance with the following reaction (Crosby,
Moilanen, and Wong 1973; Jensen and Renberg 1973).
Cl
Cl
Cl
CI2
-------
These competing reactions are predominant only with acidic
pentachlorophenol, however. Heating the sodium salt of pentachlorophenol
produces OCDD in essentially quantitative yield (World Health Organization
1977).
Except for pentachlorophenol, once a predioxin is formed, there are apparently
no competing reactions other than its reversal into the precursor. In one test, when
Irgasan DP-300, a predioxin (see Section 3, p. Ill), was heated to 980°C, only
two classes of compounds were created: dioxins and precursor molecules (Nilsson
et al. 1974).
The competing reactions clearly indicate why dioxins generally are formed only
in trace quantities and why they appear in a complex mixture with polymers and
other multiring structures, many of which are also toxic. It has been more difficult
to explain why dioxins other than the one predicted by theory are also found in
these mixtures. In the laboratory, for example, a predioxin for 2,8-DCDD created
a small amount of this dioxin when heated; however, the principal dioxin formed
was 2,7-DCDD (Boer et al. 1971).
NaO Cl
It was originally believed that such unexpected dioxins were created by arbitrary
transfers of chlorine that occurred within the energetic predioxin molecules (Boer
et al. 1971). More recent work has demonstrated that a long-recognized chemical
phenomenon known as the "Smiles rearrangement" is often operational during
dioxin creation, in which one of the rings spontaneously reverses into its mirror
image at the instant of ring closure (Gray et al. 1976; March 1968). This
rearrangement fully explains the reaction shown above, and researchers can now
predict with some certainty which dioxins will be formed from specific precursors
or predioxins. Even this development has not satisfied all observational evidence,
however, especially with the more highly chlorinated dioxins. Some researchers
believe that an equilibrium process is at work, in which dioxins slowly lose or gain
chlorine atoms to approach the most stable mixture of compounds (Rawls 1979;
Miller 1979; Ciaccio 1979).
Predioxin formation does not ensure dioxin formation (Jensen and Renberg
1972; Jensen and Renberg 1973). Pentachlorophenol attains equilibrium with its
precursor in a reversible reaction but forms large amounts of dioxins only in the
presence of an alkali (Langer et al. 1973). Irgasan DP-300 can be chlorinated and
otherwise modified chemically without inducing ring closure (Nilsson et al. 1974;
Yang and Pohland 1973). "High amounts" of predioxins have been found in
commercial products in which no dioxin could be detected. Another study revealed
predioxin concentrations as much as 20 times greater than dioxin concentrations
(Jensen and Renberg 1972). In still another study, the concentration of
hydroxypolychlorodiphenyl ethers (predioxins plus isopredioxins) was more than
50 times the dioxin concentration (Deinzer et al. 1979 ; Chemical Engineering
1978). Although not specifically noted in published literature, predioxin formation
appears to be more likely than dioxin formation. It is possible that steric or
electronic hindrances interfere with the final step of ring closure, and that
predioxins may be formed under less-rigorous reaction conditions.
Minimum Conditions for Dioxin Formation
Since dioxins usually are formed only in low yields, the minimum conditions
leading to their formation are poorly defined. Heat, pressure, photostimulation,
10
-------
and catalytic action have all been shown to encourage the reactions from
chlorinated precursors to predioxins and then to dioxins.
The temperature required for dioxin formation is variously reported at values
from 180° C to 400° C (Milnes 1971; Langer, Brady, and Briggs 1973; Crossland
and Shea 1973; Gribble 1974; Buser 1978). As previously noted, sodium
pentachlorophenate is converted to essentially pure OCDD at approximately
360° C (Langer et al. 1973). The same series of tests indicated decomposition of
several other chlorinated dioxin precursors at temperatures from about 310° to
370° C, with formation of varying quantities of dioxins (Langer et al. 1973).
Essentially quantitative formation of many different dioxins from chlorinated
catechols and o-chloronitrobenze'nes has been achieved at 180° C (Gray et al.
1976; March 1968). Direct combustion of herbicides or impregnated sawdust can
create dioxins (Nilsson et al. 1974; Langer, Brady, and Briggs 1973; Stehl and
Lamparski 1977; Ahling and Lindskog 1977; Jansson, Sundstrom, and Ahling
1978), especially if there is a deficiency of oxygen (Chem. and Eng. News 1978), but
the temperature of formation under these conditions cannot be measured (this
phenomenon may be limited to formation of dioxins from pentachlorophenol;
reports are indefinite). Apparently no definitive study has determined the
temperature of formation of 2,3,7,8-TCDD.
Pressure is needed to retain some precursor compounds in the liquid state to
permit dioxin formation (Jensen and Renberg 1972). At atmospheric pressure, the
boiling point of many precursors is apparently lower than the temperature needed
to form dioxins, and therefore the precursors escape from the reaction vessel before
decomposition reactions can occur.
Irradiation of pentachlorophenol with ultraviolet light has caused the formation
of OCDD (World Health Organization 1977; Crosby, Moilanen, and Wong 1973;
Plimmer et al. 1973; Crosby and Wong 1976). Irradiation of 2,4-dichlorophenol,
however, energized the hydrogen atom at position 6 of one ring and created a
predioxin as a principal product, but ring closure apparently did not occur
(Plimmer et al. 1973). This experiment also produced a dihydroxy biphenyl,
probably through the competing reaction described previously. It has been
postulated that although dichloro, trichloro, and tetrachloro dioxins may be
formed by irradiation, they do not accumulate because they decompose rapidly by
the same mechanism (Crosby, Moilanen, and Wong 1973). As outlined in Section
5, the less-chlorinated dioxins are unstable when exposed to ultraviolet light.
In laboratory production of dioxins, catalysts have been used to increase
reaction rates and reaction yields. Powdered copper, iron or aluminum salts, and
free iodine have been used (Pohland and Yang 1972; World Health Organization
1977), and all of these are known to stimulate many reactions of chlorinated
organic compounds (Wertheim 1939). One report indicates that heavy metallic ions
may decrease decomposition temperature (Langer et al. 1973). Presence of heavy
metals may, however, only encourage competing reactions; the silver salt of
pentachlorophenol, for example, decomposes at about 200° C to yield
polymerized materials but no dioxins (Langer et al. 1973).
Formation of dioxins is an exothermic reaction (Langer et al. 1973) that releases
heat as the molecules contract into a more compact arrangement. No published
data define the amount of heat created by formation of the various dioxins.
Once formed, the dioxin nucleus is quite stable. Laboratory tests have shown
that it is not decomposed by heat or oxidation in a 700° C incinerator, but pure
compounds are largely decomposed at 800° C (Ton That et al. 1973). A recent
report states that the nucleus survives intact through incineration up to 1150° C
(Crummett of Dow Chemical Company indicates temperature should be 1050° C )
if it is bound to paniculate matter (Rawls 1979; Miller 1979; Ciaccio 1979).
Chlorinated dioxins lose chlorine atoms on exposure to sunlight or to some types
of gamma radiation, but the basic dioxin structure is largely unaffected (Crosby et
al. 1971; Buser, Bosshardt, and Rappe 1978). In comparison with almost any other
11
-------
organic compound, the biological degradation rate of chlorinated dioxins is slow,
although measured rates differ widely (Zedda, Cirla, and Sala 1976; Commoner
and Scott 1976b; Matsumura and Benezet 1973; Huetter 1980).
LABORATORY PREPARATIONS OF DIOXINS
The first report of intentional preparation* of this class of compounds occurred
in 1872, when Merz and Weith described the preparation of
"perchlorophenylenoxyd" by thermolysis of potassium pentachlorophenate (1).
Hugounenq (1890) reported that the treatment of pentachloroanisole (2) with
concentrated sulfuric acid also gives "perchlorophenylenoxyd."
PERCHU)ROPHENYUH(WD
OCHfc
Soon after these reports, Zinke (1894) and Blitz (1904) showed that heating
heptachlorohexenone (3) to 200° C gave "perchlorophenylenoxyd." Not until
1960 was it shown that "perchlorophenylenoxyd" is octachlorodibenzo-p-dioxin
(OCDD) (4) (Denivelle 1960).
200°C
Cl
The mechanism of the reactions reported by Zinke and Blitz remained unknown
for over half a century. In 1961 Kulka showed that heptachlorocyclohexenone (3)
eliminates a molecule of hydrogen chloride at about 180° C to give
hexachlorocyclohexadienone (5). Kulka proposed that this compound, on heating
* According to scientists of Dow Chemical Company (Rawls 1979). dioxins have been prepared since
"Prometheus stole fire from the gods and brought it to mankind
12
-------
to 200° C, loses a chlorine radical to give the pentachlorocyclohexadienone
radical (6) (or its resonance isomer, the pentachlorophenoxy radical (7)), which
\then dimerizes to give (4) and a molecule of chlorine.
Cl
The mechanism that Kulka proposed, supplemented with earlier work by
Denivelle (1959, 1960), initiated numerous reports on the preparation of
halogenated dibenzo-p-dioxins under neutral or acidic conditions. A number of
these reactions are listed in Table 3.
Bayer (1903) patented a process for the preparation of dibenzo-p-dioxin (8) from
sodium o-chlorophenylate (9). This procedure, which is an extension of the earlier
work reported by Merz and Weith (1872), is based on Ullmann's preparation of
diphenylamines (Ullmann 1903) and is generally referred to as a modified Ullmann
condensation (Aniline 1973). Although the yields of the modified Ullmann reaction
rarely exceed 30 percent, this procedure was standard for the preparation of both
substituted and unsubstituted dioxins until the early 1970's. Examples of the
utilization of this process are given in Table 4, showing minor as well as major
products of reaction, where applicable.
13
-------
TABLE 3. PERHALO DIBENZO-p-DIOXINS VIA FREE
RADICAL REACTIONS
Item Reactant Conditions Product (Yield) Ref.
OH
Cl
O Cl Cl
250°-3QO°C CIV^:r
25min Cl
Cl Cl c, c,
Iflg
OH Cl Cl
REFLUXING Cl
+ CI2 1,2,4 TRICHLOROBENZENE
I6h Cl
Cl Cl Cl
25g 18g
(B3S) c
ci-^x^ci
Cl Cl
Cl Cl
0-'""0- CIY\°YVC'
Cl'
270°-280°C
30min
.V'V"
(73%) c
Cl Cl
OH
Cl Cl
Cl
25g
OH
Cl
OH
Br
OH
Cl
(continued)
Br,
1,2,4 TRICHLOROBENZENE Cl
REFLUX IBh Cl
1,2,4 TRICHLOR05ENZENE
REFLUX IBh CI^N^C
Cl
Br
/""A
CK"N^^CI\or Br2/ Br'
Cl 320°-360°c Br
•'£ 35min
Cl
Cl /or Cl
Cl Cl
0.2g
30m in
14
(52%) c
Cl Cl
Cl Cl
Cl
Br
(52*) C
(15g)
Br
Br Br
(15g)
Br Br
-------
TABLE 3 (continued)
Item Reactant Conditions Product (Yield)3 Ref.
OH
Cl
300°C
Cl Cl
Cl Cl
Cl
Cl
Cl Cl
Cl Cl
Cl Cl
Cl Cl
260-280°C
Cl Cl
Cl Cl
Cl Cl
Cl
Cl
OH
Cl
200g
OH
Cl Cl
75g
O
Cl
222g
CICI
62g
120-200°C
Cl Cl
120-200°C
Cl Cl
Cl Cl
ci xxW o ^Ax^ ci
Cl Cl
(continued)
15
-------
TABLE 3 (continued)
Item
Reactant
Conditions
Product (Yield) Ref.
OH
QUINOLINE
Cl
Cl Cl
Cl Cl
a—If no yield is stated, no value is reported in reference
b—Kulka 1965
c—Kulka 1961
d—Demvelle, Fort, and Pham 1959
e—Gribble 1974
f—Sandermann, Stockmann, and Casten 1957
g—Kaupp and Klug 1962
TABLE 4. ULLMANN CONDENSATION REACTIONS
Item
Reactant
Conditions
Product (Yield)3 Ref.
CH3
CH3
220°, I0h
CH
[i :i ii \ <*« b
^^
CH3
CH3
CH3
CH30
OK
Cu, Cu(OAc)2
190-200°C
Cu, Cu(OAc)2
CH3
CH3
OCH3
(continued)
OCH3
16
-------
TABLE 4 (continued)
Item
Reactant
Conditions
Product (Yield)3 Ref.
,OK
Br
OK
OCH3
OK
OCH3
OCH3
CH30
(continued)
CH3O
^^-Ov^^Sj-X
1&J&
OCH3
ONa
160°C
Cl
.Cl
Cl
ONa
160°C
Cu
1h
-OK
-Br
1BO°-220°C
CU,
110mm
POK
I
Cu
3h
(0.2g) 9
OK Br
+
Br KO
3.5g
4.5g
190"C
Cu
2h
(O.OSg) h,i
(0.0
17
-------
TABLE 4 (continued)
Item
Reactant
Conditions
Product (Yield) Ref.
3.5g
,-Br
"OH
OCH3
Br CH3O
SOH
5.78g
4.5g
OH
Cl
ci
3.25g
3.25g
(continued)
19D°C
Cu
2h
180°C
30min
KOH, Cu
30nun
200°C
Cu
2h
200°C
Cu
Cu
1.5h
(TRACE)
(0.164g) j
OCH3
O
O
OCH3
(0.287g)
OCH3
(0.132g)
(20mg)
Br
(40mg) k
Br
,Br
Br-
(40mg) k
18
-------
TABLE 4 (continued)
Item
Reactant
Conditions
Product (Yield) Ref.
Br
1.75g
l.5h
Br
Br
(40mg) k
Cl
Cl
3.7g
210°C (f^
0.3g Cu
3H Cl
I 1 II I (O.Bg) I
OK
CU
4h
(25%) I
OK
2g
195°C
Cu POWDER
30m in
CH3
CH3
OK
CH3
lOg
200°C
Cu POWDER,
1.5h
OCH3
(250mg) m
OCH3
Br
OH
1g
(continued)
Cu POWDER
Ih
145°C
Cu POWDER, PYRIDINE
2.5h
Br
Br
Br
Br
(3'lg) n
(Iflmg) n
19
-------
TABLE 4 (continued)
Item Reactant Conditions Product (Yield)3 Ref.
CH3
CH3 CH3
U5°C CH3v
Cu POWDER, PYRIDINE
3h CH3X%^
CH3
1.17g
(8mg) o
CH3 CH3
Cl
Cl
OK
ci
ci
ci
290°C
l-4h
'CI
Cl Cl
Cl
Cl
Cl
Cl Cl
Cl
Cl Cl
OK
® A^. +
Cl
OK
Cl
Cl
290°C
1-4h
Cl
Cl Cl
Cl
C'TYA
^Y^o-'kAci
Cl
(continued)
20
Cl Cl
°'li0
Ci"Y°
Cl Cl
-------
TABLE 4 (continued)
Item Reactant Conditions Product (Yield)3 Ref.
OK OK
(27) M I +
Cl
OK
Cl
Cl
Cl
OK
I
Cl
290°C
l-4h
290°C
l-4h
Cl
Cl
Cl
Cl
Cl Cl
ci v/W o x' c '
ci ci
Cl
Cl
Cl
Cl
Cl
Cl Cl
(continued)
Cl
Cl
Cl Cl
O'
Cl
Cl
CI'^^O'
Cl Cl
21
-------
TABLE 4 (continued)
Item
Reactant
Conditions
Product (Yield)3 Ref.
OK
Cl
Cl •'"""•^•"XII
Cl
OK
Cl Cl
OK
'
Cl
Cl
Cl
OK
Cl
Cl
Cl
Cl 29D°C
l-4ti
Cl
290°C
l-4h
290°C
1-4h
Cl
ci
Cl
Cl
OK
OK
Cl
Cl
Cl
Cl Cl
Cl
290°C
l-4h
Cl Cl
Cl
Cl
(continued)
22
-------
TABLE 4 (continued)
Item Reactant Conditions Product (Yield) Ref.
OK
Cl
29D°C
Cl C!
Cl
OK OK
Clxic'+Clxi01
CI^Xj^^CI CI^-^^CI
Cl
290°C
!-4h
Cl
OK
OK
®Clx^4^CI s^s-CI
TT + /T
Cl-^^^ci ci^V^^d
Cl
Cl
290°C
1-4h
(continued)
23
-------
TABLE 4 (continued)
Item Reactant Conditions Product (Yield) Ref.
OK
OK
_. Cl^xW^01
® JQCCI + |AACI
ci-^y^ci ci/\^
290°C
l-4h
Cl
Cl
.Cl
Cl
Cl Cl
OK
OK
ci
Cl
(continued)
290°C
l-4h
Cl Cl
Cl
Cl
Cl
ci
Cl
Cl
Cl
Cl
Cl
Cl
Cl
.Cl
Cl
Ci Cl
(MINOR)
Cl Cl
Cl Cl
Cl
Cl Cl
24
-------
TABLE 4 (continued)
Item
Reactant
Conditions
Product (Yield) Ref.
CI
29D°C
1-4h
a—If no yield is stated, no value is reported
in reference.
b—Cullinane and Davies 1936.
c—Tomita 1933.
d—Tomita and Tani 1942
e—Julia and Baillarge 1953
f—Tomita, Nakano, and Hirai 1954.
g—Tomita and Yagi 1958
h—Fujita and Gota 1955.
i—Fujita et al. 1956.
j—Inubushi et al. 1959.
k—Tomita, Ueda, and Nansada 1959.
I—Denivelle, Fort, and Hai 1960.
m—Ueda 1962.
n—Ueda and Akio 1963.
o—Ueda 1962
p—Buser 1975
As the reactions in Table 4 show, dioxins have been formed from the alkali metal
salts of ortho-halophenols through pyrolysis at temperatures of 200° to 300° C
for several hours, usually in the presence of copper powder or copper salts. Entries
23 and 24 in Table 4 show that much milder conditions (pyridine as the base and a
temperature of only 145° C for 2 to 3 hours) can give significant concentrations of
dibenzo-p-dioxins (Ueda 1963).
The mechanism for this type of reaction was generally believed to involve a
nucleophilic attack of the phenoxy ion on a second phenolate ring (Buser 1975),
followed by expulsion of the halide to give the o-halophenoxyphenate (1_0)
(predioxin). An intramolecular nucleophilic aromatic substitution followed by
expulsion of a halide gives the dibenzo-p-dioxin (H).
X- leaving group
(e.g. CI, F, Br, I, NC^, SO3R)
M=alkali metal cation
Y=any substituent group
25
-------
In 1974 Cadogan, Sharp, and Trattles proposed a more reasonable mechanism
involving the a -ketocarbene (12), which is attacked by the phenoxide to give (10).
12
10
They also proposed that the conversion of the o-halophenoxyphenate to
dibenzo-p-dioxin occurs via a benzyne intermediate (1J3).
The evidence in favor of this mechanism is quite convincing since both ortho-
and meta-halophenoxyphenates are converted to the same dibenzodioxin, as
shown below.
As shown in Table 4 (items 5, 6, 11, 13, 25-28, and 31-35), complex mixtures
result from attempts to prepare unsymmetrical dibenzo-p-dioxins using the
modified Ullmann reaction. An early attempt to circumvent this problem involved
the synthesis of a protected form of the unsymmetrical predioxin intermediate (14)
(Tomita 1938) followed by its conversion to the dioxin in a separate procedure as
shown on the next page (Tomita 1938; Keimatsu 1936).
26
-------
HBr
O O
CH3 CH3
I HBr
HOAc
HO OH
This procedure has the advantage of giving a single dibenzo-p-dioxin isomer;
however, it is limited in that yields of the dioxin rarely exceed 10 percent (Tomita
1938).
A newer and more general procedure for the preparation of unsymmetrical (as
well as symmetrical) dibenzo-p-dioxins involves the reaction of catechol salts with
ortho-dihalobenzenes in dimethylsulfoxide (DMSO) (Portland 1972; Kende 1974).
DMSO
REFLUX
This procedure is a modification of a much earlier approach to the synthesis of
dibenzo-p-dioxin, which suffered low yields (Tomita 1932) or no dioxin formation
(Fujita 1955). The improved process gives very high yields of dibenzo-p-dioxins
when dimethylsulfoxide is used as the solvent. Whether this result is simply a
solvent effect or DMSO plays a chemical role in the reaction has not been
determined. Examples of the utilization of this reaction for the preparation of
d'benzo-p-dioxins are included in Table 5.
TABLE 5. CATECHOL-BASED REACTIONS
Item
Reactant
Conditions
Product (Yield) Ref.
200°C
Cu POWER
CuN03
3ti
190°C
Cu POWDER
2h
(NO REACTION)
27
-------
TABLE 5 (continued)
Item
Reactant
Conditions Product (Yield)8 Ref.
OH
OH
KOH
DMSO,A
Br
H
3H B
Br
Br
I
OH
OH Cl
OH Cl
Cl
Cl
KOH
DMSO.A
KOH
DMSO,
KON
DMSO,A
-Br
(41*) e
Cl
OY^
II I (31X) e
O"\^^ri
Cl
OH
OH
OH
OH
Cl
Cl
ci
Cl
KOH
DMSO,
KOH
DHSO,
KOH
DMSO,
ci
Cl
Cl
Cl
Cl
^
Y
Cl
Cl
(35?.
TOTAL)
TOTAL)
(continued)
28
-------
TABLE 5 (continued)
Item
Reactant
Conditions
Product (Yield)3 Ref.
CH3
Cl
KOH
DMSO, A
KOH
DNSO, A
CH3
0
Br
Br
KOH
Cl
Cl
Cl
KOH
DMSO,A
KOH
DMSO,A
Cl
Cl
ci4
KOH
DMSO,A
t — Evenly distributed carbons
t — Preparation of uniformly labelled I4C TCDD
isomers(148 millicurie/millimole)
a — If no yield is stated, no value is reported
in reference
b — Tomita 1932
c — Fujita and Gota 1955.
d—Pohland and Yang 1972
e — Kende et al 1974
f — Rose et al 1976
Although no mechanistic studies of this reaction have been reported, it is clear
that the initial attack of the catechol dianion on the polyhalobenzene does not
occur via a benzene intermediate, since in item 3 of Table 5 one would expect two
different dioxins, which is not the result. This does not preclude the possibility that
a benzyne intermediate is involved in the conversion of the predioxin (15) to the
2,3-dichlorodibenzo-p-dioxin (16), as has been proposed for similar predioxin
cyclizations (Cadogan 1974).
29
-------
16
ONLY OBSERVED PRODUCT
NOT OBSERVED
Numerous approaches to the preparation of substituted dioxins are based on
elaboration of the dibenzo-p-dioxin skeleton via electrophilic aromatic
substitution reactions. These applications are summarized in Table 6.
TABLE 6. SUBSTITUTION REACTIONS
Item
Reactant
Conditions
Product (Yield)3 Ret.
654
+ Br
Br2 Fe(Br)3,CAT.
+ CI2
Br
Br
Cl
Cl
Cl
(continued)
30
-------
TABLE 6 (continued)
Item Reactant Conditions Product (Yield)3 Ref.
c'2
Cl ^x^r- O v^^x Cl
(LOW) b
+ PENTA-CDD AND TRI-CDD
Clx^/5^0vX^CI
(4H) c
Cl
I T II I («*> '
Br=
il J 11 J <"»> <=
+ TRITIUM CAT
Cl
T
T
T
+ CI2 FeCI3,l2(CAT)
Cl
T
OCH3
Br2
OCH3
OCH3 Br
Br OCH3
NO2
(continued)
31
-------
TABLE 6 (continued)
Item
Reactant
Conditions
Product (Yield) Ref.
HN03
HOAc,0°C
'
cr
\^o
+RCOCI
O
O
\\
H2/Pd
NH,
NH2
HONO.CuCI
O
9.2g
O
O
CI2, HOAc
t.PHENyLITHIUM
2.Br2
KBr
KBrOn.HOAc, 120°C
Br
dg)
de)
(4M)
4.6
Br2,HOAc, 120°C
Br2,HOAc, 120°C
Br*.
Br'
CI2, FeCI3, I2
(2Dg) k
(continued)
32
-------
TABLE 6 (continued)
Item
Reactant
Conditions
Product (Yield)3 Ref.
Br
50mg
O
0.5g
0.2g
Br2, H0»c
CI.
j, I2
(BOing) I
(0.7gj m
Br,
(1.54g) m
a—If no value is stated, no value is reported g—Tomita 1937.
in reference.
b—Oilman and Dietrich 1957
c—Kende et al 1974
d—Vinopal, Yamamoto, and Casida 1973.
e—Ueda 1963
f—Tomita 1935.
h—Ueo 1941
i—Gilman and Dietrich 1957
j—Oilman and Dietrich 1958
k—Sandermann, Stockmann, and Casten 1957
I—Tomita, Ueda, and Nansada 1959
m—Denivelle, Fort, and Hai 1960.
As indicated in Table 6, electrophilic aromatic substitution occurs first at
position 2. (The dioxin numbering sequence is shown in item 1.) If the newly
introduced substituent is deactivating (halogen or nitro), the next attack occurs at
either position 7 or 8. Gilman (1957, 1958) found that position 1 can be metalated
by treatment of dibenzo-p-dioxin with alkyl or phenyllithium reagents allowing
this position to be substituted.
Miscellaneous Dioxin Preparations
Buser (1976) has developed a method for the preparation of qualitative
standards of polychlorinated dioxins based on the photodechlorination of
octachlorodioxin (Crosby 1971, 1973). Irradiation of octachlorodibenzo-p-dioxin
yields a mixture of tri-, tetra-, penta-, hexa-, and heptachlorodibenzo-p-dioxin that
is useful for the analysis of materials suspected to contain polychlorodioxins.
Lester and Brennan (1972) have patented a process for the direct conversion of
substituted phenols to substituted dibenzo-p-dioxins with a palladium-copper
catalyst.
33
-------
Hmmol PdCI2
340mmol CuCI,
OH
lOOmmol NaOAc
HOAc. REFLUX
R = H, CH3, CH2CH3, OCH3, NO2
Although the mechanism of the reaction has not been studied, the reaction is
important in light of the widespread industrial uses of phenol and phenol
derivatives.
An interesting procedure for preparation of dihydroxydibenzo-p-dioxins is
based on the oxidative coupling of polyhalocatechols found by reduction of the
resulting quinone (Frejka 1937).
NaNO,
HOAc,H2O
Cl
Although the yields from this process are modest (15 to 35 percent), the reaction
proceeds under very mild conditions.
Discussion of Reaction Chemistry
On the basis of the data presented thus far, certain generalizations can be made
about the conditions under which formation of dioxins (both halogenated and
nonhalogenated) is probable.
First, and most likely, is the formation of dioxins on treatment of o-halophenols
with base at elevated temperatures. The strength of the base required to effect this
reaction depends on the particular phenol involved; however, there is adequate
precedent for the ability of relatively weak organic bases such as pyridine or
quinoline to effect dioxin formation. The temperature range required for dioxin
formation varies with the particular o-halophenol; however, 1 percent yields of
halogenated dioxins have been formed at temperatures as low as 145° C. (See Table
4, item 23.)
The presence of an ortho-halogen on the phenolic starting material is not an
absolute requirement for dioxin formation. According to the mechanism proposed
34
-------
by Cadogan, Sharp, and Trattles (1974), all that is required is a substituent ortho to
the phenol that is capable of acting as a leaving group.
Dioxins
Other substituents should be capable of elimination to give the a -ketocarbene
and thus dioxins. Among those in addition to the halogens are sulfonic acids,
sulfonate esters, nitro groups, and carboxylate esters.
A second possible source of dioxins is the treatment of halogenated phenols with
reagents conducive to the formation of the corresponding polyhalogenated
phenoxy radical (i.e., treatment with halogens or other mild oxidizing agents).
Although this reaction has been used only for the preparation of perhalo dioxins
(in yields of more than 80 percent and 200-gram quantities), there is no reason why
the reaction could not produce the lower halogenated derivitives of dioxins. (See
Table 3, item 2.)
A common practice in the preparation of polyhalobenzenes by electrophilic
halogenation is neutralization of the acid byproduct with alkali hydroxides. This
process (or simply a basic wash of product during the isolation procedure) can lead
(via nucleophilic substitution) to a halogenated phenol, which upon distillation
may produce dioxins.
Dioxins
The treatment of catechol salts with o-dihalobenzenes is a particularly efficient
method for the formation of dioxins, both halogenated and nonhalogenated. Also,
the treatment of polyhalocatechols with mild oxidants can produce significant
quantities of halogenated dihydroxy-dioxins.
Of particular concern is the treatment of aromatic compounds under oxidizing
conditions at elevated temperature. Several industrial processes involve the
oxidation of benzene, toluene, and naphthalene under "semicombustion"
conditions. In light of the studies such as that by Dow Chemical Company (Rawls
1979) on combustion sources of dioxins, the "tars"from these processes (which are
often generated in considerable quantities) deserve further study.
The mechanistic aspects of dioxin formation discussed in this section represent
the current understanding of these reactions; however, several experimental
observations about dioxin formation cannot be explained by the current theories.
The formation of four isomers of hexa-CDD on pyrolysis of 2,3,4,6-
tetrachlorophenate (Higginbotham 1968; Langer 1973), including the 1,2,3,7,8,9-
hexa-CDD (Buser 1975), can be explained in terms of the predioxin intermediates,
(17) and (19), undergoing the Smiles rearrangement as shown on the following
page.
As the diagram shows, the initially formed predioxin intermediate can proceed
directly toward dioxin formation (path a) or can undergo the Smiles
rearrangement (path b), which leads to new predioxin intermediates 1_8 and 20. The
newly formed predioxins can then react further to give a different dioxin or can
undergo the Smiles rearrangement to regenerate the original predioxin. This
35
-------
interconvertability of predioxins often leads to mixtures of dioxin products which
are otherwise difficult to understand.
An equally disturbing mechanistic point is the observation that numerous
pesticides are contaminated by polychlorodioxins, which would not be anticipated
on the basis of the feedstock materials and reaction conditions. An example
reported by Fishbein (1973) is the presence of significantly higher concentrations of
hepta- and octachlorodioxins than hexachlorodioxin in commercial 2,3,4,6-
tetrachlorophenol, also known as Dowicide-6 (see Table 9 on page 58).
The Dow Chemical Company (Rawls 1979) has proposed that the
polychlorodibenzo-p-dioxins undergo disproportionation and establish an
equilibrium mixture of halogenated dioxins. No experimental evidence in support
of this proposal has been published.
NaCI
Cl
1,2,3,7,8,9-HEXA ODD
r
Cl Cl
1,2,4,6,8,9-HEXA ODD
36
-------
SECTION 3
SOURCES OF DIOXINS
This section discusses in detail the possible sources of dioxins. The first
subsection deals with the basic organic chemicals with the greatest potential for
byproduct formation of dioxins. Subsequent subsections examine chlorophenols
and their derivatives, hexachlorobenzene, dioxins in particulate air emissions from
combustion, dioxins in plastic, and dioxins produced for research.
ORGANIC CHEMICALS
Because of the very large number of organic compounds and their varying
proclivities to form dioxins, the compounds were screened initially on the basis of
molecular structure, process sequence, and commercial significance.
As a means of focusing attention on those organic chemicals most likely to be
associated with the formation of dioxins, they were placed in the following
classifications:
Class I—Polyhalogenated phenols, primarily with a halogen ortho to the
hydroxyl group, with a high probability of dioxin formation. Products with such
compounds appearing as intermediates are also considered. Manufacture of
these materials normally involves reaction conditions of elevated temperature
plus either alkalinity or free halogen presence, either of which is conducive to
formation of halogenated dioxins.
Class II—Ortho-halophenols and ortho-halophenyl ethers where the
substituted groups are a mixture of halogens and nonhalogens. Processing
conditions are similar to those defined for Class I and produce mixed
substituted dioxins. The distinction between Classes I and II is arbitrary and
does not indicate necessarily a difference in likelihood of dioxin formation.
Class III—Other chemicals having the possibility, but less likelihood, of
dioxin formation. These include 1) ortho substituted aromatic compounds
requiring an unusual combination of reaction steps to produce dioxins, 2)
aromatic compounds that might form dioxins because of their production under
semicombustion conditions, and 3) products that might contain dioxins by way
of contamination of their starting materials.
Since only commercially significant products are of interest in this study, the
listing is limited to those produced in quantities in excess of 1000 pounds per year
and/or whose sales reach $1000 per year, as required for listing in the Stanford
Research Institute Directory of Chemical Producers. The product lists are based
on commercial production during the past 10 years.
Table 7 lists and classifies commercial organic chemicals selected as having a
relationship to dioxin formation or presence. Structures are shown for Classes I
and II, the chemicals of primary importance. Class III compounds are listed by
name only. In addition, Tables A1-5 in Appendix A give further information on
the producers and production sites of organic chemicals.
Most of the organic chemicals considered are used as manufacturing
intermediates or at least are subjected to subsequent formulation or fabrication.
37
-------
Thus further processing may introduce additional possibilities for dioxin
formation, contamination, and exposure not contemplated within the scope of this
study.
Toxicity of the many substituted dibenzo-/>-dioxins varies widely. None are
excluded from consideration here since disproportionation and other composition
shifts may bring about changes from lower toxicity forms to higher (Buser 1976).
The intended reaction mechanisms for each Class I organic chemical are shown
in Figures 2 through 12. The sequence is shown from left to right across the top of
each figure, and the possible dioxin side reaction mechanism diverges to typical
dioxin byproducts at the bottom of the figure. The specific dioxin products shown
are those for which reasonably straightforward mechanisms can be postulated. In
many cases more complex and secondary mechanisms may produce dioxins in
addition to those shown.
TABLE 7. ORGANIC CHEMICALS RELATED TO DIOXIN FORMATION
Class I
OH
4-BROMO-2,5-DICHLOROPHENOL
2-CHLORO-4-FLUOROPHENOL
DECABROMOPHENOXYBENZENE
OH
2,4-DIBROMOPHENOL
2,3-OICHLOROPHENOL
(continued)
38
-------
TABLE 7 (continued)
Class I (continued)
2,4-DICHLOROPHENOL
2,5-DICHLOROPHENOL
2,6-DICHLOROPHENOL
3,4-DICHLOROPHENOL
PENTABROMOPHENOL
2,4,6-TRIBROMOPHENOL
(continued)
39
OH
Cl
Ct
OH
Cl
Cl
OH
OH
Cl
Cl
OH
Br
OH
Br
-------
TABLE 7 (continued)
Class I (continued)
2,4,5-TRICHLOROPHENOL
Class II
BROHOPHENETOLE
0-BROMOPHENOL
2-CHLORO-1,4-DIETHOXY-5-NITROBENZENE
5-CHLORO-2,4-DIMETHOXY-ANILINE
CHLOROHYDROQUINONE
(continued)
OH
Cl
Cl
OC2H5
-Br
OH
Br
OC2H5
Cl
O2N
OC2H5
NH2
Cl
OCH3
OCH3
OH
Cl
OH
40
-------
TABLE 7 (continued)
Class II (continued)
0-CHLOROPHENOL
OH
Cl
2-CHLORO-4-PHENYLPHENOL
4-CHLORORESORCINOL
2.6-DIBROMO-4-NITROPHENOL
OH
OH
Cl
OH
NO2
3,5-DICHLOROSALICYLIC ACID
COOH
OH
2,6-DIIODO-4-NITROPHENOL
(continued)
41
OH
NO,
-------
TABLE 7 (continued)
Class II (continued)
3 ,5-DIIODOSALICYLIC ACID
0-FLUOROANISOLE
OCH3
0-FLUOROPHENOL
TETRABROMOBISPHENOL-A
HO
OH
TETRACHLOROBISPHENOL-A
Cl
Class III
3-Amino-5-chloro-2-hydroxybenzenesulfonic acid
2-Amino-4-chloro-6-nitrophenol
o-Anisidine
Benzaldehyde
Bromobenzene
o-Bromofluorobenzene
(continued)
42
-------
TABLE 7 (continued)
Class III (continued)
o-Chlorofluorobenzene
3-Chloro-4-fluoro-nitrobenzene
3-Chloro-4-fluorophenol
4-Chloro-2-nitrophenol
Chloropentafluorobenzene
2,4-Dibromofluorobenzene
3,4-Dichloroaniline
o-Dichlorobenzene
3,4-Dichlorobenzaldehyde
3,4-Dichlorobenzotrichloride
3,4-Dichlorobenzotrifluonde
1,2-Dichloro-4-nitrobenzene
3,4-Dichlorophenyhsocyanate
3,4-Difluoroaniline
o-Difluorobenzene
1,2-Dihydroxybenzene-3,5-disulfonic acid, disodium salt
2,5-Dihydroxybenzenesulfonic acid
2,5-Dihydroxybenzenesulfonic acid, potassium salt
2,4-Dmitrophenol
2,4-Dinitrophenoxyethanol
3,5-Dinitrosalicyhc acid
Fumaric acid
Hexabromobenzene
Hexachlorobenzene
Hexafluorobenzene
Maleic acid
Maleic anhydride
o-Nitroanisole
2-Nitro-p-cresol
o-Nitrophenol
Pentabromochlorocyclohexane
Pentabromoethylebenzene
Pentabromotoluene
Pentachloroaniline
Pentafluoroaniline
o-Phenetidine
Phenol (from chlorobenzene)
1-Phenol-2-sulfonic acid, formaldehyde condensate
Phenyl ether
Phthahc anhydride
Picric acid
Sodium picrate
Tetrabromophthalic anhydride
1,2,4,5-Tetrachlorobenzene
Tetrachlorophthalic anhydride
Tetrafluoro-/rj-phenylenediamine
Tribromobenzene
1,2,4-Trichlorobenzene
2,4,6-Trinitroresorcmol
43
-------
4-BROMO-2,5-DICHLOROPHENOL
Cl
2,7-DCOD
2,8-DCDD
2,7-DB-3,8-DCDD
Figure 2. Proposed reaction mechanism for dioxin formation
in the production of 4-bromo-2,5-dichlorophenol.
44
-------
2 - CHLORO - 4 - FLUOROPHENOL
2,7 - DFDD
Figure 3. Proposed reaction mechanism for dioxin formation
in the production of 2-chloro-4-fluorophenol
45
-------
DECABROMOPHENOXYBENZENE
Br y Br
Br
PENTHBROMOPHENOL
Figure 4. Proposed reaction mechanism for dioxin formation
in the production of decabromophenoxybenzene.
46
-------
2,4 - DIBROMOPHENOL
OH
PHENOL
Br
+ OTHER BROMOPHENOLS
o
o
2,7-DBDD
+ OTHER BROMOPHENOXY RADICALS
Br
+ OTHER BROMODIOXINS
Figure 5. Proposed reaction mechanism for dioxin formation
in the production of 2,4-dibromophenol.
47
-------
O 2,3-DICHLOROPHENOL
o
Cl
1,2,3-TRICHLOROBEMZEHE
Cl
Figure 6. Proposed reaction mechanism for dioxin formation
in the production of 2,3-dichlorophenol
48
-------
2,4 - DICHLOROPHENOL
Cl
CATALYST
PHENOL
+ OTHER 1SOMERS
+ OTHER CHLOROPHENOXY RADICALS
+ OTHER EHLORODIOXIHS
2,7 - DCDD
Figure 7. Proposed reaction mechanism for dioxin formation
in the production of 2,4-dichlorophenol.
49
-------
1,2,4 - TRICHLOROBENZENE
2,5 - DICHLOBOPHENOL
2,8-DCDD
2,7-DCDD
Figure 8. Proposed reaction mechanism for dioxin formation
in the production of 2,5-dichlorophenol.
50
-------
2,6 - DICHLOROPHENOL
OH
+ OTHER ISOMERS
+ OTHER CHLOROPHENOXY RADICALS
1,6 - DCDD
+ OTHER CHLORODIOXINS
Figure 9. Proposed reaction mechanism for dioxin formation
in the production of 2,6-dichlorophenol.
51
-------
3,4-DICHLOROPHENOL
Cl
Cl OH
S03H T 0 S03H
S03
H2SO4 ^
ci 2 T ci
Cl Cl
1.3,4-TRICHLOROBENZENE
S03H
Cl
|H3P04
2,7 - DCDO
Figure 10. Proposed reaction mechanism for dioxin formation
in the production of 3,4-dichlorophenol.
52
-------
PENTABROKOPHENOL
Br2 , CATALYST Br
OBDD
Figure 11. Proposed reaction mechanism for dioxin formation
in the production of pentabromophenol.
53
-------
2,4,6 - TRIBROMOPHENOL
OH
PHENOL
Br2
+ OTHER BROMOPHENOLS
Br
Br
Br
Br
Br
+ OTHER BROMOPHENOXY RADICALS
Br
+ OTHER BROMOOIOXINS
Br
2.4,1.9-TBDD
Figure 12. Proposed reaction mechanism for dioxin formation
in the production of 2,4,6-tribromophenol.
54
-------
PESTICIDE CHEMICALS
Pesticides are the most significant group of organic chemicals in relation to
dioxin occurrence. This statement is based on the structure and reaction
mechanism analogy, reaction conditions, detected presence of dioxins in a number
of commercial pesticide products, and a history of environmental contamination
problems, particularly with trichlorophenol and 2,4,5-T.
Chlorinated dibenzo-p-dioxins are known to be present in at least trace amounts
in a number of pesticide chemicals. These include 2,4,5-T, silvex, 2,4-D, erbon,
sesone, DMPA, ronnel, tetradifon, and the various chlorophenols(Fishbein 1973).
In addition, the chemical structures, reactions, and process conditions for a
number of others indicate dioxin content potential.
This study deals with production of the basic pesticide chemicals. Thus it does
not address problems of dioxin formation possibly resulting from formulation,
storage, distribution, and utilization of the pesticides. If exposure to alkaline
formation media or elevated temperatures is encountered in any of the diverse
procedures for handling and use of these pesticides, dioxin formation could be a
significant problem. •
Selection and Classification
The pesticide chemicals were selected for evaluation in this study on the basis of
molecular structure, from those listed as commercial pesticides in the Farm
Chemicals Handbook. The primary criterion was an ortho-halophenolic structure,
or the derivative esters and salts thereof. Also considered were ortho dihalo
aromatic structures, which conceivably could convert to phenols upon exposure to
alkaline conditions.
A second criterion was a minimum commercial production level of 1000 pounds
or $1000 value per year. These correspond to the minimum levels required for
inclusion in the Stanford Research Institute Directory of Chemical Producers,
which was a primary reference. The lists are based on production during the past 10
years.
The pesticide chemicals considered in this study are listed in Table 8. They are
grouped into classes representing likelihood of dioxin formation, as follows:
Class I—Highly likely to be associated with the presence of halogenated
dibenzo-p-dioxins because of the presence of an ortho-halogenated phenol in the
reaction sequence, with subjection to elevated temperature (;>I45° C+) plus
either alkalinity or the presence of free halogen.
Class II—Reasonable but lesser probability of such dioxin association because
of the presence of phenolic or aromatic structures related to dioxins; although
not directly involving dioxin precursive conditions, such chemicals might form
dioxins under irregular operating conditions.
TABLE 8. LIST OF PESTICIDE CHEMICALS
General name Chemical name
Class I
Bifenox Methyl-5-[2,4-dichloroephenoxy]-2-
nitrobenzoate
Chloranil 2,3,5,6-Tetrachloro-2,5-cyclorhexadiene-
1,4-dione
(continued)
55
-------
TABLE 8. (continued)
General name
Chemical name
2,4-D and esters and salts
2,4-DB and salts
Dicamba
Dicamba, dimethylamine
salt
Dicapthon
Dichlofenthion
Disul sodium (sesone)
2,4-DP
Erbon
Hexachlorophene
Isobac 20
Nitrofen
Pentachlorophenol (PCP)
and salts
Ronnel
Silvex and esters and salts
2,4,5-T and esters and
salts
Class II
Bromoxynil and esters
(continued)
(2,4-Dichlorophenoxy) acetic acid and
esters and salts
2,4-Dichlorophenoxybutyric acid and salts
3,6-Dichloro-2-methoxybenzoic acid
3,6-Dichloro-2-methoxybenzoic acid,
dimethylamine salt
Phosphorothioic acid o-(2-chloro-4-
nitrophenyl) o,o-dimethyl ester
Phosphorothioic acid o-2,4-dichlorophenyl
o,o-diakyl ester
2;4-Dichlorophenoxyethyl sulfate,
sodium salt
2-[2,4-Dichlorophenoxy] propionic acid
2,2-Dichloropropanoic acid 2-(2,4,5-
tnchlorophenoxy) ethyl ester
2,2'-Methylene bis (3,4,6-tnchlorophenol)
2,2'-Methylene bis (3,4,6-tnchlorophenol),
monosodium salt
2,4-Dichlorophenyl-p-nitrophenyl ether
Pentachlorophenol and salts
Phosphorothioic acid, o,o-dimethyl
0-(2,4,5-trichlorophenyl) ester
2-(2,4,5-Tnchlorophenoxy) propionic
acid and esters and salts
(2,4,5-Tnchlorophenoxy) acetic acid
2,3,4,6-Tetrachlorophenol
2,4,5-Trichlorophenol
o-Benzyl-p-chlorophenol
3,5-Dibromo-4-hydroxybenzonitrile
56
-------
TABLE 8. (continued)
General name
Chemical name
Carbonphenothion
DCPA
Dichlone
Dinitrobutylphenol,
ammonium salt
Loxynil
Lindane
MCPA
MCPB
Mecoprop
Parathion
PCNP
Piperalin
Propanil
Tetradifon
Phosphorodithioic acid s-[[(4-chloro-
phenyl)thio]methyl] o,o-diethyl ester
2,3,5,6-Tetrachloro-1,4-benzenedi-
carboxylic acid dimethyl ester
2,3-Dichloro-1,4-haphthalenedione
2,4-Dinitro-6-sec-butyl phenol,
ammonium salt
3,5-Diiodo-4-hydroxybenzonitrile
1,2,3,4,5,6-Hexachlorocyclohexane,
gamma isomer
(4-Chloro-o-toloxy) acetic acid
4-(2-Methyl-4-chlorophenoxy) butyric
acid
2-(4-Chloro-2-methylphenoxy) propionic
acid
Phosphorothioic acid o,o-diethyl o-(4-
nitrophenyl) ester
Pentachloronitrobenzene
Pipecolinopropyl-3,4-dichlorobenzoate
3-(2-Methylpiperidino)propy 1-3,4-
dichlorobenzoate
3,4-Dichloropropionanilide
1,2,4-Trichloro-5-[(4-chlorophenyl)-
sulfonyl] benzene
2,3,6-Trichlorobenzoic acid
2,3,6-Trichlorophenylacetic acid and
sodium salt
Trnodobenzoic acid
Chemical Reactions
Higher chlorinated dioxins have been detected in samples of a number of
pesticides produced from 1950 to 1970. Data from these analyses were summarized
by Fishbein (1973), as shown in Table 9.
57
-------
TABLE 9. HIGHER CHLORINATED DIOXINS FOUND IN
COMMERCIAL PESTICIDES3
Sample
Chlorodibenzo-p-dioxin detected b Number Number
Pesticide Tetra- Hexa- Hepta- Octa- contaminated tested
Phenoxyalka noates
2,4,5-T ++ ++ - 23 42
Silvex + 1 7
2,4-D + 1 24
Erbon ++ 1 1
Sesone + 1 1
Chlorophenols
Tri- - + + + 4 6
Tetra- -++++++ 3 3
Penta-(PCP) - ++ ++ ++ 10 11
Others0 _+++++ 5 22
a—Fishbem 1973
b—Concentration range ++ = >10 ppm
+ = 0 5 to 10 ppm
- = <0 5 ppm
c—DMPA, ronnel, and tetradifon were found to contain chlorodioxm contamination
Many of the dioxins present differ from those expected on the basis of the
straightforward mechanisms hypothesized. Possible reasons for this may be that
other mechanisms are at work or that substantial disproportionation is occurring
among the dioxins initially formed, as has been suggested by Dow Chemical
Company (Rawls 1979) and others (Buser 1976).
Reaction mechanisms for the Class I pesticide products are shown in the
following figures. The intended product reaction sequence is from left to right
across the top of each figure, and the possible dioxin side reaction mechanism
diverges to typical dioxin byproducts at the bottom of the figure. The specific
dioxin products shown are those for which reasonably straightforward
mechanisms can be postulated. In many cases, more complex and secondary
mechanisms may produce dioxins in addition to those shown, as evidenced by their
analytical detection in a number of products (Fishbein 1973).
The initial reaction steps in producing many of the Class I pesticides are very
similar and thus the pesticides are grouped by common mechanism. Similarity is
noted in 2,4,5-T, silvex, ronnel, 2,4-D, erbon, sesone, dichlofenthion, dicapthon,
bifenox, and dicamba. The final substitution pattern differs in each case, as does
the precise halophenol or chlorobenzene starting structure.
The first step in production of 2,4,5-T, silvex, ronnel, and erbon is identical
(Figures 13 through 16). Treatment of 1,2,4,5-tetrachlorobenzene with caustic
yields 2,4,5-trichlorophenol. The reaction conditions are sufficiently drastic,
including alkalinity and elevated temperature, to cause formation of the a -
ketocarbene, which reacts with the chlorophenylate to give the predioxin, which
then reacts to yield 2,3,7,8-TCDD. Continued alkaline processing, which occurs
with each of these product items, also contributes to the same transient
intermediates and consequently to formation of 2,3,7,8-TCDD.
58
-------
2,4,5-T
Cl
ESTERS
Figure 13. 2,4,5-Trichlorophenol, 2,4,5-T and esters and salts.
59
-------
SILVEX
Cl
ESTERS
AMINE
SALTS
Figure 14. Silvex and esters and salts
60
-------
2,4,5-TBI-
CHLOROPHENOL
RONNEL
Cl
©ONa©
' Cl
SPCI3
Cl
Figure 15. Ronnel.
61
-------
(DISUL SODIUM) SESONE
A = H o O
ii ii
OH OC2H4OS-OH OC2H4OS-ONa
6H>,,V r, VCNa§H ^ 'C' °
OH
X=H or Cl
Cl
OCH2CH2O-C-CCI2CH3
Cl
,, . ERBON
Cl
.Cl
Cl
Figure 16. Erbon and sesone.
62
-------
The normal reaction sequences for 2,4-D, 2,4-DB, 2,4-DP, disul sodium
(sesone), dichlofenthion, bifenox, and nitrofen (sequences shown in Figures 16
through 22) are analogous in their early steps to those of 2,4,5-T and others in the
group just described, but occur via 2,4-dichlorophenol rather than 2,4,5-
trichlorophenol. The dioxin formation sequence is likewise analogous but typically
would produce 2,7-DCDD.
Note that the reaction mechanism for disul sodium is presented in the same
figure (Figure 16) with that for erbon. This placement is not meant to imply that
they are co-products, but rather is intended to demonstrate the analogous reaction
patterns of typical pesticides differing as to halogenation and substitutions. Similar
analogies can be drawn among nearly all of the pesticide chemicals studied.
Another point, important to dioxin formation, is demonstrated in Figure 17,
showing the reaction for 2,4-D. The reaction sequence conventionally cited is
chlorination of phenol to 2,4-dichlorophenol, followed by a reaction with
chloroacetic acid in the presence of caustic to produce 2,4-D. This last step with the
dichlorophenol under alkaline conditions can result in dioxin formation. An
alternative process sequence cited in the patent literature (Manske 1949) reverses
the order of chlorination, as shown in the upper tier reaction of Figure 16. This
sequence would be expected to reduce the likelihood of dioxin formation. A
commercially feasible yield in excess of 80 percent is noted, but the extent of
commercial utilization is not known. This reaction sequence could possibly be
adapted to other dihalogenated phenoxyalkanoates, with an expected reduction in
dioxin formation.
Dicamba (Figure 23) with its dimethylamine salt presents one of the more
complex dioxin derivation patterns because of the continued alkaline conditions
under which various substitutions are made. First, preparation of 2,5-
dichlorophenol and its subsequent further exposure to caustic results in transient
intermediates and predioxins that form 2,7-DCDD and 2,8-DCDD. In addition,
similar alkaline processing of the carboxyl and methyl substituted forms can result
in variously substituted dioxins, only two of which, for simplicity, are shown in
Figure 23.
Pentachlorophenol (PCP), a commercially high-volume chemical, can be
manufactured by two basic methods. One involves direct chlorination of phenol
(Figure 24) in the presence of an A1C13 catalyst. The presence of normal excess
chlorine is conducive to formation of a free-radical intermediate, then of the
predioxin, and ultimately of OCDD. The alternative process based on caustic
treatment of hexachlorobenzene (Figure 25) produces chlorinated transient
intermediates analogous to the 2,4,5-T series but fully chlorine substituted. These
in turn form the predioxin and finally OCDD.
The complex free-radical mechanism by which chloranil is made (Figure 26)
results in transient intermediates similar to those occurring as byproduct
derivatives of PCP. Therefore, OCDD should be expected as a dioxin
contaminant.
Hexachlorophene and its sodium salt, Isobac 20 (Figure 27), are produced from
2,4,5-trichlorophenol whose preliminary production from 1,2,4,5-
tetrachlorobenzene is carried out by reaction with caustic. This first step
potentially forms dioxin precursors similar to the equivalent step in the
manufacture of 2,4,5-T. Consequently, 2,3,7,8-TCDD is the anticipated byproduct
dioxin.
The production of 2,3,4,6-tetrachlorophenol (Figure 28) by chlorination of
phenol would be expected to yield trace byproducts of various isomeric
hexachlorodibenzo-p-dioxins via a free-radical mechanism.
Again, because of the analytical evidence of many dioxins other than those
hypothesized in these mechanisms, no specific dioxin presence should be presumed
or excluded.
63
-------
PHENOL
OH
PHENOXYJCET1C ACID
OCH2COOH
NaOH rp^i
Cl CHaCOOH ^? v C|
CL
OH
2.4- D
Cl
OCH2COONa\ OCH2COOH
NaOH
CICH2COOH\
ESTERS
i*A/H
Cl
2.4-DICHLOROPHENOL
Cl
Cl
2 AMINE
SALTS
O QONa©
-CI
Figure 17. 2,4-D and esters and salts
64
-------
2.4-DB
OH
2,7 - DCOD
Figure 18. 2,4-DB.
65
-------
2,4 - DP
OH
ci
I
H
I
CH3-C-CO2H
O
NaOH, CH3CH -CO2H
CI
CI
2,4 - OICHLOROPHENOL
Figure 19. 2,4-DP
66
-------
c i~-
o vo
o
N
.1
-------
61FENOX
M = Na. K
X= Cl, Br
= H or Alkyl
Cl
Figure 21. Bifenox.
68
-------
OH
Cl N02
2,4-DICHLOROPHEKOL CHLORO-4-NITROPHENOL
Cl
Figure 22. Nitrofen.
69
-------
1,2,4-TRICHLOROBENZENE 2,5-OICHLOROPHENOL
Figure 23. Dicamba.
70
-------
PENTACHLOROPHENOL(PCP)
PCP, Na SALT
I Cl
OCQD
Figure 24. Pentachlorophenol (PCP) via phenol.
71
-------
PENTACHLOROPHENOL (PCP)
CI
©Na
CI ^ CI
CI
CI
CI
o Y -ci
ci ci
ci t ci
Ov^^-CI
OXY^"
CI CI
OCDD
Figure 25. Pentachlorophenol (PCP) v\a hexachlorobenzene.
72
-------
CHLORANIl
(REACTION VIA COMPLEX \
FREE RADICAL MECHANISM/
HCI , O2
220-260°C
BENZENE
Figure 26. Chloranil.
73
-------
HEXACHLOROPHENE
ISOBAC 20
Cl
2,3,7,8-TCDO
Figure 27. Hexachlorophene and Isobac 20.
74
-------
2,3,4,6 - TETRACHLOROPHENOL
OH
OH
01. JL Cl
CI2 .CATALYST
Cl
+ OTHER CHLOROPHENOLS
+ OTHER CHLOROPHENOXY RADICALS
Cl
HEXA-COD'S
Figure 28. 2,3,4,6-Tetrachlorophenol.
75
-------
Table 10 summarizes the primary raw materials involved in the production of the
Class I pesticide chemicals.
A more complete discussion of many of these pesticides appears in the following
subsections.
TABLE 10. PESTICIDE RAW MATERIALS
Pesticide product
Raw materials
Bifenox
Chloraml
2,4-D and esters and salts
2,4-DB and salts
Dicamba
Dicapthon
Dichlofention
Disul sodium (sesone)
2,4-DP
(continued)
2,4-Dichlorophenol
3-Halo-o-nitrobenzoic acid ester
NaOH
Benzene
Hydrogen chloride
Oxygen
Phenol
Chloroacetic acid
NaOH
CI2
Alcohols (for esters)
Amines (for amine salts)
Phenol
CI2
NaOH
Butyrolactone
Alcohols (for esters)
Amines (for amine salts)
1,2,4-Trichlorobenzene
NaOH
C02
Dimethyl sulfate
2-Chloro-4-nitrophenol
NaOH
Chlorodimethylthiophosphonate
2,4-Dichlorophenol
NaOH
Chlorodimethylthiophosphonate
2,4-Dichlorophenol
NaOH
Ethylene oxide
Chlorosulfomc acid
2,4-Dichlorophenol
2-Chloropropionic acid
NaOH
76
-------
TABLE 10. (continued)
Pesticide product
Raw materials
Erbon
1,2,4,5-Tetrachlorobenzene
NaOH
Ethylene oxide
2,2-Dichloropropionic acid
Hexachlorophene and
Isobac 20
1,2,4,5-Tetrachlorobenzene
NaOH
Ethylene oxide
Nitrofen
2,4-Dichlorophenol
Chloro-4-nitrobenzene
KOH
Pentachlorophenol (PCP)
Phenol
CI2 (Phenol route)
or
Benzene
CI2 (Hexachlorobenzene route)
NaOH
Ronnel
1,2,4,5-Tetrachlorobenzene
NaOH
Phosphorus sulfochloride
NaOCH,
Silvex and esters and salts
1,2,4,5-Tetrachlorobenzene
NaOH
Chloropropionic acid
Alcohols (for esters)
Amines ('or amine salts)
2,4,5-T and esters and salts
1,2,4,5-Tetrachlorobenzene
NaOH
Chloracetic acid
Alcohols (for esters)
Amines (for amine salts)
2,3,4,6-Tetrachlorophenol
Phenol
Cl,
2,4,5-Tnchlorophenol
1,2,4,5-Tetrachlorobenzene
NaOH
77
-------
DIOXINS IN COMMERCIAL CHLOROPHENOLS
AND THEIR DERIVATIVES
Since most reports of dioxins are associated with chlorinated phenolic
compounds, this section examines this group of organic materials with respect to
their reported dioxin contaminants and their utilization, manufacture, production
volumes, and derivatives. Similar information is presented, when available, for
hexachlorobenzene, which has been found to contain dioxins, and also for a group
of other related commercial chemicals that theoretically could contain dioxin
contaminants, although no analyses have been reported. For each chemical, the
discussions include the probable processing steps that may promote dioxin
formation and also the mechanisms through which dioxins could appear in the
associated process wastes or be retained within the chemical products.
Chlorophenols
Chlorinated phenols area family of 19 compounds, consisting of a benzene ring
to which is attached one hydroxyl group and from one to five chlorine atoms. The
positions of the chlorine atoms with respect to the hydroxyl group and to each
other provide the opportunity for three monochlorophenols, six each of dichloro-
and trichlorophenols, three tetrachlorophenols, and one pentachlorophenol.
Many researchers have established the presence of dioxins in these chemicals;
Table 11 lists the results of several such studies.
Data in this table show that until recently dioxins have not been found in
commercially produced mono- or dichlorophenols. The presence of 2,3,7,8-TCDD
in low concentration was found in 1979 in a railroad tank car spill of o-
chlorophenol. One or more samples of all chlorophenols with three or more
chlorine atoms that have been examined have contained dioxins. TCDD's have
been identified not only in the 2,4,5-trichloro isomer but also in the 2,4,6-trichloro
isomer. One or more samples of trichlorophenol have contained dioxins with two
to eight chlorine substituents. Only dioxins with six to eight chlorine substituents
have been found in tetra- and pentachlorophenol. Numerous analyses have
confirmed that dioxins with less than six chlorine substituents are not found in
pentachlorophenol.
Most commercial chlorophenols are used as raw materials in the synthesis of
other organic compounds. Some of the less highly chlorinated phenols are used
with formaldehyde to make fire-resistant thermosetting plastics (Doedens 1964).
Those containing three or more chlorine atoms are used directly as pesticide
chemicals. 2,4,6-Trichlorophenol is effective as a fungicide, herbicide, and
defoliant (Hawley 1971). It was formerly used in large quantities in the leather-
tanning industry; however, its use in this industry has decreased substantially (U. S.
Environmental Protection Agency 1978a), probably as a result of the improved
effectiveness and mass production of 2,4,5-trichlorophenol, a substance of
sufficient importance to warrant a special section in this report. 2,3,4,6-
Tetrachlorophenol is used as a preservative for wood, latex, and leather, and also
as an insecticide (Kozak et al. 1979).
Pentachlorophenol or its sodium salt is said to be the second most widely used
pesticide in the United States. It is effective in the control of certain bacteria, yeasts,
slime molds, algae, fungi, plants, insects, and snails. Because of its broad spectrum,
pentachlorophenol is used in many ways:
• As a preservative for wood, wood products, leather, burlap, cordage, starches,
dextrins, and glues
• As an insecticide on masonry for termite control
78
-------
TABLE 11. CHLORODIOXINS REPORTED IN CHLOROPHENOLS
Chlorodioxins (-CDD's), ppma
Chlorophenol sample mono-CDD's DCDD's
Monochlorophenol
2-chlorophenol
o-chlorophenol
Dichlorophenol
2,4-dichlorophenol
2,6-dichlorophenol
Trichlorophenol
2,4,5-tnchlorophenol
(1969)
2,4,5-trichlorophenol
(1970)
2,4,5-tnchlorophenol
(1970)
2,4,5-tnchlorophenol
(1970)
Na-2,4,5-trichlorophenol
(1967)
Na-2,4,5-tnchlorophenol
(1969)
2,4,5-tnchlorophenol
2,4,6-trichlorophenol
trichlorophenol
ND
-
ND
ND
ND
ND
ND
ND
ND
ND
-
ND
-
ND
-
ND
ND
ND
ND
ND
ND
ND
0.72 (2,7)
-
ND
-
tri-CDD's
ND
-
ND
ND
ND
ND
ND
ND
ND
ND
-
93 (2,3,7)
-
TCDD's penta-CDD'
ND
0037(2,3,7,8)"
ND
ND
030(1,3,6,8)
6 20 (2,3,7,8)
ND
ND
007 (2,3,7,8)
ND
1 40 (2,3,7,8)
0.30(2,3,7,8)
49(1,3,6,8)
ND(05)
ND
-
ND
ND
ND
1.5
ND
ND
ND
ND
-
ND
-
s hexa-CDD's
ND
-
ND
ND
ND
ND
ND
ND
ND
ND
-
ND
05-10
hepta-CDD's OCDD
ND
-
ND
ND
ND
ND
ND
ND
ND
ND
-
ND
0.5-10
ND
-
ND
ND
ND
ND
ND
ND
ND
ND
-
ND
05-10
Data source
Firestone 1 972
Chemical Week 1 979
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1 972
Firestone 1972
Firestone 1 972
Elvidge 1971
Firestone 1972
Woolson et al 1972
(continued)
-------
TABLE 11. (continued)
Chlorodioxins (-CDD's), ppma
Chlorophenol sample mono-CDD's DCDD's tri-CDD's TCDD's penta-CDD's hexa-CDD's hepta-CDD's OCDD Data source
00
o
Tetrachlorophenol
2,3,4,6-tetrachlorophenol - - -
(Dowicide 6)
2,3,4,6-tetrachlorophenol ND ND ND ND ND
2,3,4,6-tetrachlorophenol ND ND ND ND ND
(1967)
2,3,4,6-tetrachlorophenol ND ND ND ND ND
tetrachlorophenol - - - ND (0 5)
Pentachlorophenol
PCP (Dowicide 7) -
PCP - ND(0.5)
Na-PCP(1967) ND ND ND ND ND
Na-PCP(1969) ND ND ND ND ND
PCP (1970) ND ND ND ND ND
PCP (1970) ND ND ND ND ND
PCP (1967) ND ND ND ND ND
PCP (1969) ND ND ND ND ND
PCP (1970) ND ND ND ND ND
PCP (1970) ND ND ND ND ND
PCP (1978) - - - ND(01)
Pentachlorophenate - - -
PCP formulation - - -
PCP (technical grade) - ND
PCP (reagent grade) - - - ND
Buser 1975
29
4 1
ND
10-100
9
10-100
14
20
39
35
0 17
13
091
15
19
_
_
33-42
0 02-0 03
5 1
ND
ND
10-100
235
100-1000
145
11 3
49
23
ND
47
2 1
23
140
+
870
19-24
0 04-0 09
0 17
ND
ND
10-100
250
100-1000
38
33
15
ND
ND
ND
53
15
432
+
50-3300
7-11
0 02-0 03
Firestone 1972
Firestone 1972
Firestone 1972
Woolson et al 1972
Buser 1975
Woolson 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Firestone 1972
Dioxin in Industrial Sludges
1978
Jensen and Renberg 1972
Jensen and Renberg 1972
Villanueva 1973
Villanueva 1973
(continued)
-------
TABLE 11. (continued)
Chlorodioxins (-CDD's), ppm3
Chlorophenol sample mono-CDD's DCDD's tri-CDD's TCDD's penta-CDD's hexa-CDD's hepta-CDD's OCDD Data source
PCP (many samples)
PCP's(17)
PCP or PCP-Na (7)
PCP(Dowicide 7 1970)
PCP (Dowicide 7 1970)
(distilled)
PCP
Na-PCP(Dowicide G 1978)
ND
9-27 90-135 575-2510 PCP—A wood preservative
1977
0-23 - 0-3600 Crummett 1975
0.03-10 0.6-180 5.5-370 Buser and Bosshardt 1976
4 125 2500 PCP Ad Hoc Study Report
12/78 SAB
10 65 15 PCP Ad Hoc Study Report
12/78 SAB
9-27 - 575-2510 Johnson etal. 1973
ND-2 1-12 4-173 Dow Chemical Company
1978
a—Key to abbreviations and symbols ND = Not detected (minimum detection level, ppm) Other numbers in parentheses indicate year chlorophenol sample was obtained, or specific dioxm
detected
- - Not analyzed or not reported
b—Presence of 2,3,7,8-TCDD confirmed but not quantitatively reported
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• Asa fungicide/ slimicide in pulp and paper mills, in cooling tower waters, and
in evaporation condensers
• As a preharvest weed defoliant on seed crops
• As a preservative on beans (for replanting only)
• Asa means of controlling slimes in secondary oil recovery injection water (in
the petroleum industry)
By far the major use of pentachlorophenol is as a wood preservative. It was once
reported to have been used in shampoos; however, this chemical does not now
appear to be used as an ingredient in cosmetics or drugs, since it is not listed either
in the CTFA Cosmetic Ingredient Dictionary (Cosmetic, Toiletry, and Fragrance
Association, Inc. 1977), or in the Physicians' Desk Reference (1978).
Manufacture—
Through either process variations or separation of mixtures by fractional
distillation, manufacturers selectively produce chlorophenols with specific
numbers and arrangements of chlorine atoms. Table 12 shows that 13 of the 19
possible chlorophenols are currently sold commercially in sufficient volume to be
listed in the 1978 Stanford Research Institute Directory of Chemical Producers.
Seven of these are made in much higher volume than the other six. The high-
volume products are all made by one of two major types of manufacturing
processes, referred to herein as the hydrolysis method and the direct chlorination
method.
As mentioned earlier, chlorophenols are benzene rings that contain one
hydroxyl group and one or more chlorine atoms. The basic raw material in the
manufacture of chlorophenols is benzene, and the two major manufacturing
methods differ primarily in the order in which the substituents are attached to the
benzene ring. In the hydrolysis method, chlorophenols are made by replacing one
chlorine substituent of a polychlorinated benzene with a hydroxyl group. The
hydrolysis method is the only practical method for producing some of the
chlorophenols, such as the 2,4,5 isomer; this isomer is apparently the only one
currently produced in large quantity by this method (Kozak 1979; Deinzer 1979;
Chemical Engineering 1978). In the direct chlorination method, phenol
(hydroxybenzene) is reacted with chlorine to form a variety of chlorophenols. Each
manufacturing method is more fully described in the paragraphs below. In
addition, a detailed description of the manufacture of 2,4,5-trichlorophenol (2,4,5-
TCP) is outlined separately.
Hydrolysis method—The first step in the hydrolysis method is the direct
chlorination of benzene. Through a series of distillations, rechlorinations, and
other chemical treatments, several purified chlorobenzene compounds are
obtained that contain from two to six chlorine substituents. Specific chlorophenols
are then made by reacting one of the chlorine substituents with caustic, thereby
replacing the chlorine atom with a hydroxyl group (see Figure 29). The reaction
takes place in a solvent in which both materials are soluble, and the mixture is held
at specific conditions of temperature and pressure until the reaction is complete.
The product is then recovered from the reaction mixture. The solvent is usually an
alcohol (most often methanol), although use of other solvents is possible.
A 1957 process patent describes the manufacture of pentachlorophenol from a
starting material of hexachlorobenzene (U.S. Patent Office 1957e). Methanol is the
solvent, and the reaction takes place at temperatures of 125° to 175° C and
pressures of 125 to 360 psi. Reaction time is 0.3 to 3 hours. This method is known to
have been used commercially (Arsenault 1976).
A variation of this process using ethylene glycol as the solvent also has been used
commercially for the production of 2,4,5-trichlorophenol (Commoner and Scott
1976a; Whiteside 1977).
82
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A process described in another 1957 patent uses water as the solvent in hydrolysis
of dichloro- and trichlorobenzenes (U.S. Patent Office 1957c). Temperature is
maintained from 240° C to 300° C under alkaline conditions at autogenous
pressure. Reaction time varies from 0.5 to 3 hours. By this method,
monochlorophenols are produced in yields greater than 70 percent from o-, m-, and
p-dichlorobenzene. Metachlorophenol is formed as an impurity from the ortho-
and para- starting materials through ring rearrangement mechanisms.
Orthochlorophenol, which is the most likely dioxin precursor, is not formed by
ring rearrangement but is produced in 86 percent yield from o-dichlorobenzene.
Also, hydrolysis of 1,2,4-trichlorobenzene forms a mixture of dichlorophenol
isomers in yields up to 95 percent.
TABLE 12. COMMERCIAL CHLOROPHENOLS AND THEIR PRODUCERS3
Chlorophenol
Manufacturer(s)
o-Chlorophenol
m-Chlorophenol
p-Chlorophenol
2,3-Dichlorophenol
2,4-Dichlorophenol
2,5-Dichlorophenol
2,6-Dichlorophenol
3,4-Dichlorophenol
3,5-Dichlorophenol
2,4,5-Tnchlorophenol
2,4,6-Trichlorophenol
2,3,4,6-Tetrachlorophenol
Pentachlorophenol
Dow Chemical Company
Monsanto Company
Eastman Kodak Company
Aldrich Chemical Company
Specialty Organics, Inc
R S.A. Corporation
Dow Chemical Company
Monsanto Company
Specialty Organics, Inc.
Dow Chemical Company
Monsanto Company
Rhodia, Inc.
Vertac, Inc.
Velsicol Chemical Corporation
Aldrich Chemical Company
Specialty Organics, Inc
Aldrich Chemical Company
Aldrich Chemical Company
Specialty Organics, Inc
Dow Chemical Company
Vertac, Inc.
Dow Chemical Company
Dow Chemical Company
Dow Chemical Company
Vulcan Materials Company
Reichold Chemicals
a—Source. Stanford Research Institute Directory of Chemical Producers, U.S 1978
83
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DIRECT CHLORINATION
VARIATIONS
EMPLOY A
CATALYST
*-
SOLVENT
UNNECESSARY
di
PHENOL MIXTURE OF CHLOROPHENOL ISOHERS
HYDROLYSIS
CATALYST
UNNECESSARY
SOLVENT REQUIRED
POLYCHLORINATED BENZENE SPECIFIC CHLOROPHENOL
Figure 29. Basic chlorophenol reactions.
A 1967 patent describes the use of a combined methanol-water solvent system
(U.S. Patent Office 1967b). Temperature is maintained at 170° to 200° C, under
above-autogenous pressures. Reaction time is 1 hour or less.
A 1969 patent describes still another solvent, dimethylsulfoxide (DMSO) (U.S.
Patent Office 1969). Use of this solvent in a mixture with water permits the reaction
to take place at atmospheric pressure; caustic hydrolysis of hexachlorobenzene to
pentachlorophenol occurs at approximately 155° C and is complete in about 3
hours. This process apparently has never been applied commercially.
When an alcohol is used as a solvent, the chemical mechanism that occurs
involves an initial equilibrium reaction between the alcohol and caustic to form a
sodium alkoxide, which is the reagent that actually attacks the chlorobenzene. The
compound formed first is the alcohol ether of the chlorophenol. On standing,
rearrangement of the compound occurs to form the chlorophenate plus any of
several side reaction products (Sidwell 1976). This mechanism is significant
because it explains the "aging" step that is a distinct phase in commercial hydrolysis
sequences, and it also explains the substantial quantity of byproduct impurities
that are derived from the alcohol solvents.
In all these processes, the product is recovered through either of two methods. In
one, extraction into benzene separates the organic materials from water, salt, and
excess caustic. Subsequent vacuum distillation reclaims the benzene for recycle and
also separates the chlorophenols into purified fractions. Extraction with benzene
(or a similar solvent) is probably the preferred product recovery method for
chlorophenols of lower molecular weight, especially the mono- and dichloro-
products, since they are more easily distilled than the heavier products.
84
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The alternative product recovery method is to filter the reaction mixture,
perhaps after partial neutralization or evaporation and subsequent cooling, to
reclaim unreacted polychlorobenzenes. The solution is then acidified and filtered
again to collect the solid products. This variation is probably best suited to
recovery of tri-, tetra-, and pentachlorophenols because these products and their
raw materials are solids at room temperature and therefore can be removed more
easily in the filtration operations.
Chlorophenols can be purified by distillation to separate high-boiling impurities.
Technical feasibility has been reported in three 1974 patents, in which purified
pentachlorophenol is recovered in good yield by high vacuum distillation in the
presence of chemical stabilizers (U.S. Patent Office 1974a, 1974b, 1974c).
Purification of 2,4,5-trichlorophenol by distillation has also been reported (World
Health Organization 1977).
The high-temperature, high-pressure, and strongly alkaline conditions of the
hydrolysis process are conducive to the formation of dioxin compounds. Although
not in present U.S. commercial use, the hydrolysis manufacture of pentachloro-
phenol was especially favorable for the formation of octachlorodibenzo-p-dioxin
(OCDD)(Figure 25, p. 72). As described in more detail later in this section, the
commercial hydrolysis method is known to produce 2,3,7,8-TCDD from 1,2,4,5-
tetrachlorobenzene.
Direct chlorination method—Direct chlorination begins by the addition of a
hydroxyl group to benzene to form hydroxybenzene or phenol. This compound is
manufactured in specialized plants, usually through sulfonation, chlorination, or
catalytic oxidation of benzene. Dioxins have not been reported as resulting from
this portion of the process; this study is therefore concerned only with the second
part of the process in which phenol is reacted with chlorine to form various
chlorophenols.
The reaction of phenol with chlorine actually forms a mixture of chlorinated
phenols (see Figure 29), although certain compounds are formed preferentially.
Direct chlorination is practical, therefore, only if the desired product is one of the
high-yield compounds. Except for low-volume specialty isomers and the high-
volume 2,4,5 isomer, all commercial chlorophenols made in this country are those
that are formed preferentially by this process (Buser 1978; Kozak 1979; Deinzer
1979; Chemical Engineering 1978). These include mono- and dichlorophenols that
are substituted at positions 2 and 4, the symmetrical 2,4,6-trichlorophenol isomer,
2,3,4,6-tetrachlorophenol, and pentachlorophenol.
Chlorination of phenol can be accomplished in batch reactors, but is best suited
to the continuous process shown in simplified form in Figure 30 (U.S. Patent Office
1960; Sittig 1969). Liquid phenol and/or lower chlorinated phenols are passed
countercurrently with chlorine gas through a series of reaction vessels. Trace
amounts of aluminum chloride catalyst are added, usually as a separate feed into an
intermediate vessel. Equipment is sized so that all the chlorine is absorbed by the
phenol; the last phenol-containing vessel is usually built as a scrubbing column to
ensure complete chlorine absorption. Gas leaving the scrubber is anhydrous
hydrogen chloride, which is either used in other chemical operations or dissolved in
water to form substantially pure hydrochloric acid as a byproduct.
The chlorophenol compound created in greatest amount by this process is
established by the ratio of feed rates of chlorine and phenol. Because all chlorine is
consumed, it is fed at rates 1 to 5 times the molecular proportion of phenol,
depending on the principal product desired. To prevent excessive oxidation that;
produces nonphenolic chlorinated organic compounds, temperatures are carefully
regulated; the usual temperatures are 130° to 190° C for pentachlorophenol and
170° C for 2,4-dichlorophenol. Pressure is atmospheric, and reaction time is 5 to 15
hours (U.S. Patent Office 1960).
85
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ID
3
u
o
-------
The mixture from the first reaction vessel can be vacuum-distilled to separate the
various compounds. Unreacted phenol and any undesired less-chlorinated phenols
would be recycled. To make some products for which purity standards are rather
flexible, very little purification is necessary, and some processes may include no
final distillation or other treatment. Also, a chlorinated product may be withdrawn
from the scrubber (usually a mixture of 2- and 4-mono- or 2,4-dichlorophenol) and
may be either distilled, with portions recycled to the first reactor for further
chlorination, or sold as is. 2,4-Dichlorophenol may be further processed to the
phenoxy herbicide 2,4-D.
Supplemental processing steps may be necessary to remove contaminants such
as "hexachlorophenol" (hexachlorocyclohexadiene-l,4-one-3), dioxins, and
furans from PCP made by this process. Hexachlorophenol may be formed during
the process by overchlorination pf the reaction mass (U.S. Patent Office 1939).
Dioxins may be formed during distillation by the condensation of PCP with itself
or with hexachlorophenol (see Table 3; see also Figure 24, p. 71).
Dioxins have been reported in numerous samples of PCP, as shown in Table 8.
Although hexa-CDD's, hepta-CDD's, and OCDD are known to be present in
commercial PCP, 2,3,7,8-TCDD has never been found (Chemical Regulation
Reporter 1978; U.S. Environmental Protection Agency 1978e).
All PCP made in the United States is produced by the direct chlorination of
phenol; apparently the method involving the hydrolysis of hexachlorobenzene has
never been used commercially for PCP production (American Wood Preservers
Institute 1977). Dow reportedly changed its production process in 1972 to produce
a PCP with lower dioxin content; the other two producers of PCP apparently have
not followed Dow's lead (Chemical Regulation Reporter 1978). Details of Dow's
process change were not reported.
Production—
Production figures for di- and tetrachlorophenols are not available. Although
current figures for pentachlorophenol production are also not available, it is
estimated from production capacity information (Table 13) that U.S.
manufacturers are producing as much as 53 million pounds of PCP annually.
Annual U.S. trichlorophenol production is probably also in the range of 50 million
pounds (Crosby, Moilanen, and Wong 1973).
As Table 12 indicates, chlorophenols are apparently manufactured by at least 11
companies, which represent two diverse groups of chemical producers. Of the 13
commercial chlorophenols, 7 are made by Dow Chemical Company in Midland,
Michigan. Except for 2,4,5-trichlorophenol, all of the isomers made by Dow are
those formed preferentially through direct chlorination of phenol. Competitive
with Dow in the sale of these seven chlorophenols are four other companies:
Monsanto Company—Sauget, Illinois
Reichold Chemicals, Inc.—Tacoma, Washington
Vulcan Materials Company—Wichita, Kansas
Rhodia, Inc.—Freeport, Texas
All of these companies are engaged for the most part in the mass production of
organic chemicals for which market demand is relatively constant. These
companies are geared to heavy chemical production, and their products are made
to commercial standards of purity and are usually sold at relatively low prices.
The other six chlorophenols are made by five companies that generally
manufacture fine or specialty chemicals:
Velsicol Chemical Corp.—Beaumont, Texas
Eastman Kodak Company—Rochester, New York
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TABLE 13. 1977 PENTACHLOROPHENOL PRODUCTION CAPACITY3
Company
Dow Chemical Company6
Monsanto Company0
Reichold Chemicals
Vulcan Materials Company
Production location
Midland, Ml
Sauget, IL
Tacoma, WA
Witchita, KN
Total capacity
1 977 Capacity
(millions of pounds)
17
26
20
16
79
a—Source American Wood Preservers Institute 1977 These figures presumably do not include
production of sodium or potassium salts of pentachlorophenol
b—Dow ceased production of the sodium salt of PCP(Dowicide G) in April, 1978 (Dow Chemical
Company 1978)
c—Monsanto stopped all PCP production as of January 1, 1978 (Dorman 1978)
Aldrich Chemical Co., Inc.—Milwaukee, Wisconsin
Specialty Organics, Inc.—Irwindale, California
R.S.A. Corporation—Ardsley, New York
Products from these manufacturers are often batch-produced under contract
with specific industrial customers, sometimes to high standards of purity. They are
manufactured in much smaller quantities than those described above, often
intermittently, and they are sold at a relatively high price. Often, the products from
these companies are used in the manufacture of Pharmaceuticals, photographic
chemicals, and similar high-quality chemical materials. Without exception, the
chlorophenols made by these companies are those not formed preferentially
through direct chlorination of phenol.
Any chlorophenol with a chlorine atom at position 2 (ortho to the hydroxyl
group) may be a precursor for dioxin formation. Nine of the 11 companies are
reported to make at least one chlorophenol of this description. Potential for the
occurrence of dioxins is therefore not limited to the manufacture of chlorophenols
for pesticide use.
It is not known, however, whether the hydrolysis method, which is especially
conducive to dioxin formation, is used to make the lower-volume chlorophenols.
In many instances, this method probably is not used because the parent
polychlorobenzenes needed for raw materials usually cannot be directly
synthesized by conventional chlorination techniques. For production of m-
chlorophenol in high yields, for example, general chemical references describe a
synthesis route that involves chlorination of nitrobenzene, followed by reduction,
diazotization, and hydrolysis of the nitrate group (Vinopal, Yamamoto, and
Casida 1973). Multistep batch processes of this type are necessary to cause the
substituents to attach to the ring at unnatural positions (Kozak 1979). These
specialized production methods are not addressed in this report.
The primary chemical producers described above are not the only commercial
sources of chlorophenols. Other companies purchase chlorophenols from primary
producers, combine them with other ingredients, and market the formulated
-------
products. Still others deal only in distribution of the chemicals or chemical
mixtures. Most often the trade name of the product changes each time it is bought
and sold.
2,4,5-Trichlorophenol
In 1972, hexa-, hepta-, and octachlorodioxins were found at concentrations of
0.5 to 10 ppm in four of six trichlorophenol samples analyzed. Tetrachlorodioxins
were not detected (0.5 ppm level of detection). The research report implies that the
2,4,5 isomer of trichlorophenol was being analyzed (Woolson, Thomas, and Ensor
1972).
Also in 1972, another study showed dioxins in trichlorophenols (Firestone et al.
1972). Isomers identified in 2,4,5-trichlorophenol (or its sodium salt) at ppm levels
were 2,7-di-, 1,3,6,8-tetra-, 2,3,7,8-tetra-, and pentachlorodioxins. High levels of
2,3,7-trichlorodioxin (93 ppm) and 1,3,6,8-tetrachlorodioxin (49 ppm) were found
in the 2,4,6 isomers of trichlorophenol. The investigator analyzed for, but could not
detect, mono-, hexa-, hepta-, and octachlorodioxins in these trichlorophenol
samples. Data from these two studies are included in Table 11 on page 79.
A U.S. EPA position document on 2,4,5-TCP (U.S. Environmental Protection
Agency 19781) was prepared to accompany the August 2, 1978, Federal Register
notice of rebuttable presumption against continued registration of 2,4,5-TCP
products. The position document gives the following description of the known uses
of this chemical:
The largest use of 2,4,5-TCP is as a starting material in the manufacture of a
series of industrial and agricultural chemicals, the most notable of which is the
herbicide 2,4,5-T and its related products including silvex [2-(2,4,5-
trichlorophenoxy) propionic acid], ronnel [0,0-dimethyl 0-(2,4,5-
trichlorophenyl)-phosphorothioate], and the bactericide hexachlorophene.
2,4,5-TCP and its salts are used in the textile industry to preserve emulsions used
in rayon spinning and silk yarns, in the adhesive industry to preserve polyvinyl
acetate emulsions, in the leather industry as a hide preservative, and in the
automotive industry to preserve rubber gaskets. The sodium salt is used as a
preservative in adhesives derived from casein, as a constituent of metal cutting
fluids and foundry core washes to prevent breakdown and spoilage, as a
bactericide/fungicide in recirculating water in cooling towers, and as an
algicide/slimicide in the pulp/paper manufacturing industry.
There are some minor uses of 2,4,5-TCP and its salts in disinfectants which are of
major importance relative to human exposure. These include use on swimming-
pool-related surfaces; household sickroom equipment; food processing plants
and equipment; food contact surfaces; hospital rooms; sickroom equipment; and
bathrooms (including shower stalls, urinals, floors, and toilet bowls).
It is apparent, therefore, that all the uses of 2,4,5-TCP exploit the poisonous
character of the compound and its derivatives. As a pesticide, it is subject to EPA
registration in all of its applications except those associated with food processing.
Manufacture—
Only trace amounts of 2,4,5-trichlorophenol are created by direct chlorination of
phenol. It can be made in about 50 percent yield by rechlorination of 3,4-
dichlorophenol (U.S. Patent Office 1956c). Neither of these production methods is
in commercial use in this country.
Domestic commercial production is accomplished through hydrolysis of 1,2,4,5-
tetrachlorobenzene, which is a principal isomer produced by rechlorination of
o-dichlorobenzene. Conversion of this chemical to the sodium salt of 2,4,5-TCP is
89
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a batch reaction with caustic soda. Subsequent neutralization with a mineral acid
forms the product. The basic process is a typical application of the hydrolysis
method of chlorophenol production described earlier. The reaction sequence is
given below:
.2.4,5-TETRACHLOROBENZENE
HCI
2,4,5-TRICHLOROPHENOL
At least three variations of the basic process have been described in process
patents specifically for production of 2,4,5-TCP, differing only in the solvents used
and therefore in the conditions needed to drive the reaction to completion. The first
patented process (U.S. Patent Office 1950) uses a solvent of ethylene glvcol or
propylene glycol at preferred temperatures of 170° to 180° C and pressures up to 20
psi. A second patent, the most recent (U.S. Patent Office 1967b), describes the use
of methanol as a solvent, with temperatures ranging from 160° to 220° C and with
pressure less than 350 psi (probably 50 to 200 psi). Both of these alcohol-based
processes require 1 to 5 hours to complete.
A third patent (U.S. Patent Office 1957b) describes the use of water as the
reaction solvent. Use of water necessitates the most severe operating
conditions: operating temperatures from 225° to 300° C and pressures from 400
to 1500 psi. This method permits greater production, since reaction time is reduced
to no more than 1.5 hours and in some instances to as little as 6 minutes. In addition
to its production efficiency, the water-based process eliminates the side reactions
between caustic and the alcohol solvents, which form undesired impurity
compounds. The process also improves product yield and eliminates solvent costs.
It appears, however, that the high-temperature, high-pressure, and strongly
alkaline conditions of the water-based process promote a continuation of the
reaction, in which 2,4,5-TCP combines with itself to form 2,3,7,8-TCDD (see
Figure 13, p. 59).
The patent examples cited above are fairly old, and details of the current 2,4,5-
TCP production methods are difficult to obtain. A 1978 EPA report on 2,4,5-TCP
briefly describes present-day 2,4,5-TCP manufacture as a reaction of
tetrachlorobenzene with caustic in the presence of methanol at 180° C under
pressure. Although a final product purification step is described in the most recent
patent example (U.S. Patent Office 1967b), the EPA report does not describe it.
A more detailed estimate of current production methods is derived from
fragmentary descriptions of both U.S. and foreign operations (Sidwell 1976; World
Health Organization 1977; Fuller 1977; Whiteside 1977; Fadiman 1979; D. R.
Watkins 1980). (One plant from which much of this information was derived
ceased production of 2,4,5-TCP in 1979.) Figure 31 is a flow chart prepared from
90
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1,2,4,5-
Tetrachlorobenzene
Sodium
Hydroxide
Alcohol
Recycle
Water
Solid
Waste
•-Air Emission
Figure 31. Flow chart for 2,4,5-TCP manufacture.
these sources, showing the most likely process details. In this processing scheme,
alcohol and caustic are mixed and heated. Tetrachlorobenzene is added, an
exothermic reaction begins, and cooling water is turned onto the reactor coils.
After all the tetrachlorobenzene has been added, the batch is "aged"; during the
aging period, sodium-2,4,5-trichlorophenate (Na-2,4,5-TCP) is formed. Volatile
compounds such as dimethyl ether also are formed during the aging step; these are
vented from the reactor, along with small amounts of vaporized methanol.
According to Vertac, Inc., dimethyl ether is absorbed by a water scrubber, in which
it is highly soluble. The presence of these flammable vapors presents a fire or
explosion hazard, and the reaction vessel is usually enclosed in blastproof walls to
minimize physical damage from any accident that may occur during the aging step.
91
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On completion of the reaction, the methanol is evaporated, condensed, and
recycled. At the same time, water is added to keep the batch contents in solution.
In this process, a toluene washing step is conducted to purify the product by
removing some of the high-boiling impurities. Toluene condensed from the
overhead of an auxiliary still is mixed into the cooled water solution of Na-2,4,5-
TCP. The mixture is then allowed to stand quietly so that the water and organic
phases can separate into layers. The organic layer, containing impurities, is
decanted and returned to the toluene still as feed. The water layer, containing
partially purified Na-2,4,5-TCP, can be used directly to manufacture a herbicide
derivative. Alternatively, hydrochloric acid can be added to neutralize the mixture.
Acidic 2,4,5-TCP precipitates and is separated from the liquid by centrifugation.
Many of the impurities created during this process, including 2,3,7,8-TCDD,
accumulate in the bottom of the toluene still. Still bottoms are removed
periodically to be discarded. Toluene still bottoms have been identified as the
source of at least one exposure of the public to dioxins, and also as the source of one
of the highest concentrations of 2,3,7,8-TCDD (40 ppm) ever discovered in such
wastes (Watkins 1979, 1980; Richards 1979a). (Analysis of this waste sample is fully
described in Section 4 of this report.)
As shown in Figure 31, the acidic 2,4,5-TCP is dried and either packaged for sale
or used to manufacture other derivative products. One reference shows one or
more stages of purification of the product after it is centrifuged from the water
solution (World Health Organization 1977). One stage of high-vacuum distillation
is conducted to create what is described as "agricultural grade 2,4,5-TCP." A
second stage of distillation removes additional impurities to form "pharmaceutical
grade 2,4,5-TCP." It is believed that all U.S. hexachlorophene is made from a
distilled grade of this chemical.
Process details concerning the only remaining 2,4,5-TCP plant in the United
States have not been released. It was reported in 1967 that this plant (Dow
Chemical Company, Midland, Michigan) was using the water-based process
described in its 1955 patent (Sconce 1959; U.S. Patent Office 1957b), but this
probably is not the case today. Another report states that the process is conducted
with very careful temperature control to prevent the formation of dioxins (Sittig
1974). This source also indicates that still bottoms from the manufacture of 2,4,5-T
at this plant are being discarded by incineration; therefore, a distillation is
presumably being performed. It is not known whether these still bottoms are from a
toluene washing still or from a product still.
Production—
Dow Chemical Company is apparently the only current producer of both 2,4,5-
TCP and Na-2,4,5-TCP. Merck and Company has recently begun producing Na-
2,4,5-TCP (Stanford Research Institute 1979). Current records related to the EPA
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) indicate that 42
companies, including Dow, are marketing 94 registered commercial products
containing 2,4,5-TCP or its salts (U.S. Environmental Protection Agency 1978i).
According to EPA sources, most, if not all, of these companies obtain the basic
chemical from Dow (Reece 1978c).
Former 2,4,5-TCP manufacturing sites are listed in Table 14 by location and
owner. Details of the processes used by these former producers are not known;
however, "still bottoms" were said to be the source that created a dioxin exposure
at Verona, Missouri (see Section 5). The methanol-based process with a toluene
washing stage was used by Vertac, Inc. (Watkins 1980).
Current U.S. production figures for 2,4,5-TCP and its salts are not available
(U.S. Environmental Protection Agency 19781). In 1970, the estimated level of
domestic production for 2,4,5-TCP and its derivatives was 50 million pounds
(Crosby, Moilanen, and Wong 1973). In 1974, the reported annual world
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TABLE 14. FORMER 2,4,5-TCP MANUFACTURING SITES3
Plant location Owner
Niagara Falls, NY Hooker Chemicals and Plastics
(approximately 45 years)b
Jacksonville, AR Reasor-Hill Corp. (1946-61)°
Hercules, Inc. (1961-71 )c
Transvaal, Inc. (1971-78)c
Verona, MO North Eastern Pharmaceuticals and
Chemicals Co
Monmouth Junction, NJ Rhodia, Inc.
Linden, NJ GAF Corp
Chicago, IL Nalco Chemical Co
Cleveland, OH Diamond Shamrock Corp.
a—Unless otherwise noted, the information in this table was derived from Stanford Research
Institute Directory of Chemical Producers, United States 1976-79, and U.S International Trade
Commission Synthetic Organic Chemicals, U S Production and Sales 1968, 1974, 1976-78.
b—Chemical Week 1979a.
c—Richards 1979a
production of all chlorophenols and their salts was estimated to be 100,000 tons, or
200 million pounds (Nilsson et al. 1974).
Chlorophenol Derivatives with Confirmed Dioxin Content
The wide utilization of chlorophenols in chemical synthesis makes it virtually
impossible to identify all the potential derivatives of this class of compounds. The
following paragraphs outline the manufacture of derivatives that, upon analysis,
have been reported to contain chlorinated dioxins. The products are all pesticides,
which are usually made as only partially purified chemicals and are intended to be
distributed rather broadly into the environment.
2,4-D, 2,4-DB, 2,4-DP, and 2,4-DEP—
The compound 2,4-dichlorophenoxyacetic acid (2,4-D) is a widely used herbi-
cide and a close chemical relative of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
described later in this section. A 50:50 mixture of these two chemicals, known as
"Herbicide Orange" (earlier called "Agent Orange"), was used as a defoliant during
the Vietnam conflict. The chemical formula of 2,4-D is shown below.
93
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The herbicide 2,4-DB is 4-(2,4-dichlorophenoxy) butyric acid; 2,4-DP is 2-(2,4-
dichlorophenoxy) propionic acid; and 2,4-DEP is tris [2 - (2,4-dichlorophenoxy)
ethyl] phosphite; all are closely related chemically to 2,4-D.
In 1972, Woolson, Thomas, and Ensor found hexachlorodioxin in one sample of
2,4-D at a level between 0.5 and 10 ppm. No other dioxins were observed. Twenty-
three other 2,4-D samples, as well as three 2,4-DB and two 2,4-DEP samples, were
analyzed, but no dioxins were found at a 0.5 ppm limit of detection. Apparently,
only tetra-, hexa-, hepta-, and octachlorodioxins were sought in these analyses.
The samples apparently were not analyzed for dichlorodioxins, which should be
more likely to occur (see Figure 17, p. 64).
According to the World Health Organization (1977), 2,4-D is widely used as a
herbicide for broadleaf weed control in cereal crops (wheat, corn, grain sorghum,
rice, other small grains), sugar cane, and citrus fruits (lemons), and on turf,
pastures, and noncrop land. Food-related uses account for 58 percent of all 2,4-D
used in the United States in 1975.
Two manufacturing processes have been described for 2,4-D, only one of which
starts with a chlorinated phenol. One process is a direct chlorination of
phenoxyacetic acid (U.S. Patent Office 1949). The other process is a reaction
between 2,4-dichlorophenol and chloroacetic acid (U.S. Patent Office 1958a). The
second process is similar to the 2,4,5-T manufacturing process described in the
following section and is also similar to the process used to make 2,4-DB (U.S.
Patent Office 1963).
Since many companies make 2,4-D and its esters and salts, both production
processes may be in use, although it is claimed that chlorination of phenoxyacetic
acid produces a higher yield and is a simpler process. In a batch reactor,
phenoxyacetic acid is melted by heating it to 100° C. With continuous agitation,
chlorine is bubbled through the molten chemical and the temperature is increased
slowly to 150° C. A stream of dry air is passed through the reactor to sweep away
the hydrogen chloride byproduct. When the calculated amount of chlorine has
been added, the resulting mass is cooled, pulverized, and packaged. No solvent is
used, no special recovery operation is needed, and product purification is
unnecessary. If dioxins are created during this process, the mechanism of their
formation is unknown.
The second process involves reaction of 2,4-dichlorophenol with chloroacetic
acid in a solvent mixture of water and sodium hydroxide. This process is said to be
used by at least one large manufacturer (Sittig 1974). Heat is applied to the vessel,
and the water is evaporated from the mixture. When the temperature begins to rise,
indicating that most of the water has evaporated, heating is stopped and a fresh
charge of cold acidified water is added. The product can be filtered from the
mixture and dried; this procedure would form an impure product.
Alternatively, the product can be extracted from the cooled mixture with a
water-immiscible solvent and then separated from the solvent by distillation. This
latter recovery method would probably create anhydrous organic wastes and
therefore is probably in use by at least one company that has been reported to
incinerate waste tars from 2,4-D manufacture (Sittig 1974).
This chlorophenol-based process for making 2,4-D could create dioxins because
it provides for an alkaline mixture of a dioxin precursor chemical in contact with
hot heating surfaces. If the product is only filtered from the reaction mixture, the
dioxin contaminants would be captured along with the product. If solvent
extraction is employed, part of the dioxin would probably appear in wastes from
the process and part would probably be captured with the product.
The process for manufacture of 2,4-DB uses 2,4-dichlorophenol and gamma
butyrolactone in a solvent mixture of dry butanol and nonane, with sodium
hydroxide as a reaction aid. The chemical reactions are shown on the following
page.
The ingredients are mixed and heated to a temperature of about 165° C for a
94
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w
A
2.4-DICHLOBOPHENOl
NaOH
CH2CH2CH2COOH
O
period that may range from 1 to 24 hours. On completion of the reaction, dilute
sulfuric acid is added and 2,4-DB precipitates; the precipitate is centrifuged from
the mixtures, dried, and packaged. Liquids from the centrifuge are allowed to stand
quietly and separate into two liquid layers. The water fraction is discarded, and the
organic layer is recycled to the subsequent reaction batch. Any water that is
brought into the reactor is removed by distillation before the next reaction is
started.
It is possible that dioxins could be produced by this process by the mixture of 2,4-
dichlorophenol with sodium hydroxide being brought into contact with a hot
surface (see Figure 18, p. 65). Product recovery methods are such that any dioxins
formed would either be removed as solids along with the product or be recycled to
the succeeding batch.
Commercial production of 2,4-D in the United States started in 1944 and by the
mid-1960's had peaked at 36 million kg (World Health Organization 1977). After
the use of Herbicide Orange was discontinued, production dropped. Production in
1974 is estimated to have been 27 million kg (World Health Organization 1977).
Production figures for 2,4-DB and 2,4-DEP are not available.
The current basic producers of 2,4-D and 2,4-DB acids, esters, and salts as
reported by Stanford Research Institute in 1978 are listed in Table 15. Former
producers or production sites are listed in Table 16. No current producers of 2,4-
DEP are listed in the Stanford Research Institute publication of 1978.
Sesone—
The chemical name for the pesticide sesone is 2-(2,4-dichlorophenoxy) ethyl
sodium sulfate. The only sample known to have been analyzed for dioxins
contained 0.5 to 10 ppm hexachlorodioxin (Helling et al. 1973). No tetra-, hepta-,
or octachlorodioxms were detected (0.5 ppm detection level). Analysis apparently
was not performed for di-, tri-, or pentachlorodioxins.
Sesone is made from 2,4-dichlorophenol by boiling it for several hours in a water
solution of beta-chloroethyl-sodium sulfate and sodium hydroxide. The following
are the chemical reactions of the process:
W (•»•)
OCH2CH2OSO3Na
© © NaOH
CICH2CH2OSO3Na »•
95
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TABLE 15. CURRENT BASIC PRODUCERS OF 2,4-D AND 2,4-DB
ACIDS, ESTERS, AND SALTS3
Pesticide
Company
Production location
2,4-D and esters Dow Chemical Company
and salts
Fallek-Lankro Corp.
Imperial, Inc.
North American Phillips Corp ,
Thompson-Hayward Chemical Co.,
subsidiary
PBI-Gordon Corp.
Rhodia, Inc.
Riverdale Chemical Co.
Union Carbide Corp , Amchem
Products, Inc., subsidiary
Vertac, Inc., Transvaal, Inc ,
subsidiary
Midland, Ml
Tuscaloosa, AL
Shenandoah, IA
Kansas City, KS
Kansas City, KS
Portland, OR
St. Joseph, MO
Chicago Heights, IL
Chicago Heights, IL
Ambler, PA
Fremont, CA
Jacksonville, AR
2,4-DB and salts Rhodia, Inc.
Union Carbide Corp , Amchem
Products, Inc , subsidiary
Portland, OR
Ambler, PA
a—Source Stanford Research Institute 1978
In more detail, the straight-chain reactant is made by combining ethylene
chlorohydrin and chlorosulfonic acid in a refrigerated water solution (U.S. Patent
Office 1958c). After partial neutralization with sodium hydroxide, 2,4-
dichlorophenol is added and the mixture is boiled for about 15 hours. According to
the patent example, the mixture is probably not purified; it is simply spray-dried to
form a usable product. It could be purified by repeated extractions with hot alcohol
to separate the sodium sulfate impurity.
The manufacture of sesone meets all of the requirements for promotion of the
formation of 2,7-DCDD (see Figure 16, p. 62). Both the raw material and the
final product contain a chlorine atom ortho to a ring-connected oxygen atom, and
the mixture is heated in the presence of sodium hydroxide. Although overall
reaction temperature is only slightly above 100° C, it could be higher at the heating
surfaces.
The volume of sesone produced annually is not known. Only nine commercial
products containing the herbicide are currently registered as pesticides with EPA.
96
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TABLE 16. FORMER BASIC PRODUCERS OF 2,4-D AND 2,4-DB
ACIDS, ESTERS, AND SALTS3
Pesticide .formerly
reported produced
Company
Production location
2,4-D acid, esters, Chempar
and salts
Miller Chemical, subsidiary of
Alco Standards
Rhodia, Inc
Thompson Chemical
Woodbury, subsidiary of Comutrix
Portland, OR
Whiteford, MD
North Kansas City, KS
St. Paul/Minneapolis, MIM
St. Louis, MO
Orlando, FL
2,4-DB and salts Rhodia, Inc.
North Kansas City, MO
St. Paul/Minneapolis, MN
a—Source- Dryden et a I. 1980
DMPA—
The chemical name for DMPA is 0-(2,4-dichlorophenyl) 0-methyl
isopropylphosphoramidothioate (Merck Index 1978). Some of the relatively
higher chlorodioxins (hexa-, hepta-, and/or octachlorodioxins) were detected at
ppm levels in at least one DMPA sample analyzed in 1972 (Helling et al. 1973).
The following is the structure for DMPA.
s
II
O-P-NHCH(CH3)2
OCH3
DMPA
Synthesis of this molecule involves the methanolysis of 0-(2,4-dichlorophenyl)
phosphorodichloridothioate, which is made through the phosphoralation of
dichlorophenol (U.S. Patent Office 1960; Blair, Kaner, and Kenaga 1963).
DMPA is known commercially as Zytron, K-22023, and Dow 1329 (Merck
Index 1978). It is useful as an insecticide, especially against houseflies (Blair,
Kaner, and Kenaga 1963). It is also useful as a herbicide for controlling the growth
of undesirable plants (U.S. Patent Office 1963; Merck Index 1978). DMPA is not
believed to be produced in large amounts. Currently three companies—Dow
97
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Chemical Company, Techne Corp., and Rhodia Chemical Company—have each
registered one DMPA pesticide product with EPA (U.S. Environmental
Protection Agency 1978f).
Trichlorophenol Derivatives—
As mentioned earlier, the largest use of 2,4,5-TCP is as a starting material in the
manufacture of several pesticide and bactericide products. Table 17 lists the known
2,4,5-TCP derivatives, their specific uses, and the companies which have recently
been reported to produce them.
2,4,5-T—The chemical name for 2,4,5-T is 2,4,5-trichlorophenoxyacetic acid
and it is the most important derivative of 2,4,5-trichlorophenol. It has been a
registered pesticide for about 30 years (U.S. Environmental Protection Agency
1978h) and was used primarily as a herbicide for controlling woody plant growth.
2,4,5-T is best known for its combined use with 2,4-D as Herbicide Orange, which
was used extensively by the U. S. military as a defoliant during the Vietnam conflict.
When the toxicity of this formulation became apparent, the government suspended
all further military use of Herbicide Orange, and in 1970 stopped many registered
domestic uses including application to lakes, ponds, ditch banks, homesites,
recreational areas, and most food crops (World Health Organization 1977). Until
1979, domestic commercial use of 2,4,5-T continued for control of brush and other
hardwood in forestry management and on power transmission right-of-ways,
rangelands, rice fields, and turfs. Most of these uses have now been suspended
(Blum 1979).
Parts-per-million quantities of dioxins have been reported in 2,4,5-T since 1970
(World Health Organization 1977). A study (Woolson, Thomas, and Ensor 1972;
Kearney et al. 1973b; Helling et al. 1973) of samples manufactured between 1950
and 1970 found 0.5 to lOppmTCDD's in 7 of 42 samples tested; an other 13 samples
contained 10 to 100 ppm TCDD's. Hexa-CDD's were found in 4 of the 42 samples.
The limit of detection in this study was reported as 0.5 ppm for each dioxin. Most
samples came from a company that no longer produces 2,4,5-T. Elvidge (1971)
reported that five of six 2,4,5-T samples contained TCDD's at levels ranging from
0.1 to 0.5 ppm. The dioxin was present in two 2,4,5-T ester samples at 0.2 to 0.3
ppm. TCDD's were also found in two 2,4,5-T ester formulations at 0.1 and 0.2
ppm. The level of detection was 0.05 ppm. Storherr et al. (1971) reported finding
0.1 to 55 ppm TCDD's in seven of eight samples of technical 2,4,5-T (see Figure 13,
p. 59).
Analysis of 200 samples of Herbicide Orange for TCDD's by the U.S. Air Force
showed 0.5 ppm or less in 136 samples and more than 0.5 ppm in the remainder.
The highest level was 47 ppm (Kearney et al. 1973). Early in 1976, investigators at
Wright State Univeristy analyzed 264 samples of U.S. Air Force stocks of
Herbicide Orange and found TCDD's at levels ranging from 0.02 to 54 ppm
(Tiernan 1975). The level of detection was 0.02 ppm.
2,4,5-T with a TCDD isomer content of less than 0.1 ppm is now commercially
available from U.S. producers (U.S. Environmental Protection Agency 1978h).
Commercial 2,4,5-T guaranteed to contain less than 0.05 ppm TCDD's is available
from foreign producers (World Health Organization 1977).
The commercial method of producing 2,4,5-T is briefly described in EPA
Position Document 1 (April 1978) on this pesticide (U.S. Environmental
Protection Agency 1978h). According to this document, 2,4,5-TCP is reacted with
chloroacetic acid under alkaline conditions. Subsequent addition of sulfuric acid
produces 2,4,5-T (acidic form), which can then be reacted with a variety of alcohols
or amines to produce 2,4,5-T esters and amine salts. The chemical reactions are as
follows:
98
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+ CICH2COONa
Na-2,4,5-TCP
HCI
A more complete description of the 2,4,5-T production process appears in a
patent record (U.S. Patent Office 1958a). Sodium 2,4,5-trichlorophenate is most
often delivered to the process as a water solution containing excess sodium
hydroxide directly from the Na-2,4,5-TCP manufacturing process. Amyl or
isoamyl alcohol, or a mixture of these solvents, is added, and heat is applied to
remove water as an azeotrope. When all water has been removed, chloroacetic acid
is added to initiate the reaction that produces sodium 2,4,5-trichlorophenoxyace-
tate (Na-2,4,5-T) and sodium chloride. The reaction proceeds under total reflux for
about 1 . 5 hours at 1 1 0° to 1 30° C and atmospheric pressure. An excess of sodium
hydroxide is present during the reaction.
Water is then fed into the reactor and distillation is resumed, this time to remove
the amyl alcohol and replace it with water. At the end of the second distillation, the
reaction mixture consists of Na-2,4,5-T dissolved in a sodium chloride brine.
The patent example incorporates a purificiation step that may not be conducted
in commercial practice. Near the end of the second distillation, activated carbon
may be added to adsorb heavy or colored impurities, which would include dioxins
that were present in the Na-2,4,5-TCP feedstock. On completion of the second
distillation, the carbon would be filtered from the mixture and discarded. If this
step is conducted, the process will generate a waste carbon sludge likely to be
contaminated with dioxins. If this step is not conducted, any dioxins present are
likely to be carried through the process and appear in the final product.
In either variation, the next step is to add acid to neutralize the residual caustic
and to form insoluble 2,4,5-T. The product is then filtered or centrifuged from the
waste brine, dried, and packaged for sale. The filtrate from this step should contain
only soluble sodium chloride and sulfate, excess neutralization acid, and very small
quantities of organic matter; it is discarded as a liquid waste.
The patent that describes the manufacture of 2,4,5-T is unusually detailed and
indicates that the temperature during the process is never above 140° C, which is
lower than the temperature believed to be necessary to create dioxins. Any dioxins
that enter with the feed will appear either in the product or in process wastes, but
additional dioxins probably are not formed during 2,4,5-T manufacture. Even
during abnormal operation or an industrial fire, it would be difficult for the
temperature to exceed by far the low boiling point of amyl alcohol, since all
operations take place in unpressurized vessels.
99
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TABLE 17. DERIVATIVES OF 2,4,5-TRICHLOROPHENOL
AND THEIR RECENT (1978) PRODUCERS3
Derivative
Use
Current producers
Production location
2,4,5-T and
esters and
salts
Herbicide for
woody plant
control
Silvex and
esters and
salts
(Fenoprop)
Herbicide for
woody plant
control, plant
hormone
Dow Chemical Company
North American Phillips
Corp., Thompson-Hayward
Chemical Co., subsidiary
FBI-Gordon Corp.
Riverdale Chemical Co.
Rhodia, lnc.b
Union Carbide Corp.,
Amchem Products, Inc.,
subsidiary
Vertac, Inc.,
Transvaal, Inc.,
subsidiary0
Dow Chemical Company
North American Phillips
Corp., Thompson-Hayward
Chemical Co.,
subsidiary
Riverdale Chemical Co.
Vertac, Inc,
Transvaal, Inc.,
subsidiary0
Erbon
Ronnel
(Fenchlorfos)
Hexachloro-
phene
Herbicide,
weed and
grass killer
Midland, Ml
Kansas City, KS
Kansas City, KS
Chicago Heights, IL
Portland, OR or
St. Joseph, MO
Ambler, PA
Fremont, CA
St. Joseph, MO
Jacksonville, AR
Midland, Ml
Kansas City, KS
Chicago Heights, IL
Jacksonville, AR
Dow Chemical Company Midland, Ml
Insecticide Dow Chemical Company Midland, Ml
Bactencide Givaudan Corporation
Clifton, NJ
a—Source. 1978 Directory of Chemical Producers, United States
b—Rhodia is not listed in the 1978 Directory of Chemical Producers, United States, but has been
recently cited by the EPA (Blum 1979) and the news media (Wall Street Journal 1979 and
Environmental Reporter 1979a) as a manufacturer of 2,4,5-T
c—In 1979 this company ceased production of 2,4,5-tnchlorophenol for subsequent conversion to
2,4,5-T and silvex
d—Although erbon is not listed in the 1978 Directory of Chemical Producers, United States, several
companies including Dow Chemical Company have registered erbon pesticide products with
the EPA Dow is most likely the basic producer of the herbicide
100
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The highest production of 2,4,5-T occurred between 1960 and 1968, when it
peaked at 16 million pounds per year (World Health Organization 1977). Between
1960 and 1970 a total of 106.3 million pounds was produced domestically (Kearney
et al. 1973b). Production declined during the 1970's because of restrictions on use
of the compound. In 1978 the annual U.S. usage of 2,4,5-T was estimated at only 5
million pounds (American Broadcasting Co. 1978). Because of EPA's March 1979
emergency ban on most of the remaining uses (Blum 1979), current usage is
believed to be even less, probably less than 2 million pounds per year.
2,4,5-T may be produced and formulated in several forms as salts and esters of
the acid. The low-volatility esters have been used most often. Emulsifiable
concentrates of 2,4,5-T salts and esters contain 2 to 6 pounds per gallon of the acid
equivalent; oil-soluble concentrates contain 4 to 6 pounds of active ingredient per
gallon (U.S. Environmental Protection Agency 1978h).
Until 1979, this herbicide was probably produced by the seven companies shown
in Table 18. Over a hundred companies were recently marketing more than 400
formulated pesticide products containing 2,4,5-T (U.S. Environmental Protection
Agency 1978h).
TABLE 18. FORMER PRODUCERS OF 2,4,5-T
(Prior to 1978)a
Company Location
Chempar Portland, OR
Diamond Shamrock Corp. Cleveland, OH
Hoffman-Taft, Inc. Springfield, MO
Hercules, Inc. Wilmington, DE
Monsanto Company St. Louis, MO
Rorer-Amchem Ambler, PA
Fremont, CA
St. Joseph, MO
Jacksonville, AR
Wm. T. Thompson Company, St Louis, MO
Thompson Chemical Division
a—Sources Stanford Research Institute Directory of Chemical Producers, United States 1976
and 1977. United States Tariff Commission/United States International Trade Commission
Synthetic Organic Chemicals, United States Production and Sales 1968, 1974, 1976, and
1977
Silvex — Silvex is a family of compounds that act as hormones to plants andean
be used as specific herbicides. Formulations containing these materials were used
for control of woody plants on uncropped land and for control of weeds on
residential lawns until 1979, when sales of most products containing silvex were
halted (Blum 1979). Silvex is still being used on noncrop areas, on rangelands and
orchards, and on rice and sugar cane (Toxic Materials News 1979b; Chemical
Regulation Reporter 1979c).
The chemical name for silvex acid is 2-(2,4,5-trichlorophenoxy) propionic acid.
It is also known as Fenoprop, 2,4,5-TP, and 2,4,5-TCPPA.
101
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Silvex is available either as the acid or esters and salts of the acid. The low-
volatility esters are probably the form most widely used.
TCDD's were detected (1.4 ppm) in one of seven silvex samples manufactured
between 1965 and 1970 and analyzed in 1972; no other dioxins were detected
(Woolson, Thomas, and Ensor 1972; Kearney et al. 1973b).
The following are recent producers of silvex as listed in the 1978 Stanford
Research Institute Directory of Chemical Producers:
Dow Chemical Company —Midland, Michigan
North American Phillips, Thompson Hayward Chemical, subsidiary—Kansas
City, Kansas
Riverdale Chemical—Chicago Heights, Illinois
Vertac, Inc., Transvaal, Inc., subsidiary—Jacksonville, Arkansas
Hercules, Inc., of Wilmington, Delaware, is a former producer (U.S. Tariff
Commission 1968). The 1978 EPA pesticide files indicate that more than 300
products or formulations containing silvex are registered (U.S. Environmental
Protection Agency 1978f).
Silvex manufacture is more complex than that of other 2,4,5-TCP derivatives.
The compounds sold commercially are usually complex esters, made from a
specialized alcohol and silvex acid. The final manufacture of the ester is well
documented in a process patent (U.S. Patent Office 1956a), as is the manufacture of
the specialized alcohol. No definitive information has been found, however, on
manufacture of the silvex acid, probably because compounds of this type can be
manufactured by a long-established chemical reaction that is used in many
categories of the organic chemical industry (J. Am. Chem. Soc. 1960). Silvex acid
would be the source of any dioxins in commercial silvex products (see Figure 14,
p. 60). The figure on the following page illustrates the most likely chemical reaction
that would form the silvex acid and also shows the subsequent esterification, as
described in the patent.
In the first step, 2,4,5-TCP is probably brought into reaction with the methyl
ester of 2-chloropropionic acid, with methanol as the solvent and sodium
methoxide as a reaction aid. This reaction would occur approximately at the
boiling temperature of methanol, which is 65° C. The resulting compound would
probably be separated from the reaction mixture by treatment with acidified water
followed by extraction with a chlorinated hydrocarbon.
The addition of more acidified water to the extractant and a subsequent
evaporation at a temperature near 100° C would hydrolyze the intermediate
.compound and also would drive off the chlorinated hydrocarbon for recycle and
the methanol byproduct to be reclaimed for other uses. The resulting compound is
2-(2,4,5-trichlorophenoxy) propionic acid, which is known to be a reactant in the
subsequent processing (U.S. Patent Office 1956a).
Other methods could be used to prepare this intermediate acid, but none of them
would utilize high temperatures or unusual solvents. The use of a strongly alkaline
hydrolysis step, rather than an acidic medium, is possible. In any method, the last
step is probably another solvent extraction using 1,2-dichloroethane to prepare the
mixture for the next operation.
Silvex acid can be converted to various esters by using selected ether alcohols.
The esterification steps are identical except for variations in the alcohol raw
material. In a solvent of 1,2-dichloroethane, with concentrated sulfuric acid as a
reaction aid, the intermediate acid is mixed with an ether alcohol. In the following
example, butoxypropoxypropanol is used. The mixture is held at about 95° C
for about 7 hours. During this period, the water formed in the reaction is removed
by passing the reflux condensate through a decanter. At the end of the reaction, the
product is present as an insoluble precipitate, which is filtered from the mixture,
washed with sodium carbonate solution, and vacuum-dried at about 90° C.
102
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COOCH3
CH3CHCOOCH3
Cl
OC4H9
I
AQUEOUS ACID
COOChfcCH^H
OC4H9
HOCH2CH2CH
0_C3H7
H2SO4
SILVEX ESTER
Although complete data are unavailable, no information indicates that
temperatures greater than 100° C would occur at any step in the manufacture of
acidic silvex or its esters. It is therefore unlikely that dioxin compounds would be
created as side reaction products.
Absence of detailed information makes it impossible to establish whether dioxin
contamination would carry through from the 2,4,5-TCP raw material into the final
product. Theoretical considerations do not permit an estimation of the degree of
purification required by the various intermediate compounds. Probably, as noted
above, at least two solvent extraction operations are used to separate the principal
processing materials from water solutions. Since TCDD's are very slightly soluble
in chlorinated organic solvents, some could be carried through these operations,
but most should be rejected.
Erbon—Very little information is available on erbon, which is derived from 2,4,5-
trichlorophenol. Analysis of one erbon sample produced in 1970 indicated more
than 10 ppm octachlorodioxin (Woolson, Thomas, and Ensor 1972).Tetra-, penta-
hexa-, and heptachlorodioxins were not detected (0.5 ppm limit of detection).
In 1978, nine companies had registered 17 products containing erbon (U.S.
Environmental Protection Agency 1978). Dow is probably the only producer of the
basic chemical. The other companies are most likely formulators who obtain their
basic erbon ingredient from Dow. The volume of erbon produced annually is not
known.
This herbicide is an ester based on 2,4,5-TCP. Although the initial
manufacturing step is not reported, the first intermediate is almost identical to that
103
-------
used to make sesin. General organic chemical references indicate that it is probably
made by an initial reaction of 2,4,5-TCP with ethylene chlorohydrin (March 1968).
Water is the most likely solvent, made strongly alkaline with sodium hydroxide,
and the intermediate probably precipitates on addition of acid and is filtered from
the solution and dried. A process patent (U.S. Patent Office 1956b) discloses that
the second reaction step is a combination of the intermediate with 2,2-dichloropro-
pionic acid in a solution of ethylene dichloride (1,2-dichloroethane), with addition
of a small amount of concentrated sulfuric acid to remove the water formed in the
reaction. These chemical reactions are shown by the following sequence drawing:
OCH2CH2OH
Cl
2,4,5-TCP
CH3CCI2COOH
H2S04
o
II
OCH2CH2O-C-CCI2CH3
Cl
Cl
ERBON
The resulting reaction mixture is partially purified by washing with water and is
then fractionally distilled under vacuum to recover ethylene dichloride for recycle
and possibly to separate the product from any impurities
The first step of the reaction is the one that could possibly form dioxins (see
Figure 16, p. 62). Both the raw material and the resulting intermediate contain a
chlorine atom ortho to a ring-connected oxygen atom, and the mixture is heated
with sodium hydroxide. Temperatures are not high, however, since water is
probably the solvent used and this simple reaction ordinarily does not require
application of pressure Dioxin formation could occur at the surface of steam coils
if high-pressure steam is used for distillation.
Apparently no operation other than the final distillation would remove any
dioxin contamination from this material Since the most likely impurities would be
more volatile than the final ester, even the distillation may not serve to isolate
dioxins into a waste stream Most dioxins either formed by the process or present in
the raw material would probably be collected with the final product.
Ronnel—The chemical name of ronnel is 0,0-dimethyl 0-(2,4,5-trichlorophenyl)
phosphoroate. This insecticide is also known by such names as fenchlorfos,
Trolene, Etrolene, Nankor, Korlan, Viozene, and Ectoral (Merck Index 1978).
104
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Ronnel is effective in the control of roaches, flies, screw worms, and cattle grubs
(Merck Index 1978). In 1972, highly chlorinated dioxins were detected at ppm
levels in an unknown number of ronnel samples (Woolson, Thomas, and Ensor
1972).
The manufacture of ronnel is a two-step process (U.S. Patent Office 1952) in
which Na-2,4,5-TCP is reacted first with thiophosphoryl chloride, then with
sodium methoxide. The chemical reactions are shown below:
ONa
PSCI3
NaOCH3
SsS/)CH3
X
In the first step, dry Na-2,4,5-TCP is added to an excess of thiophosphoryl
chloride (2 to 4 times the theoretical amount) and heated slightly, perhaps to 80° C.
Sodium chloride is formed as an insoluble precipitate; it is filtered from the mixture
and discarded. The clear filtrate is vacuum-distilled to recover the excess
thiophosphoryl chloride for recycle and to fractionally separate the intermediate
from side reaction impurities.
In a separate reaction vessel, metallic sodium is mixed with methanol. Hydrogen
gas is liberated, creating a methanolic solution of sodium methoxide. This solution
is mixed slowly with the purified intermediate while the mixture is maintained at
approximately room temperature with noncontact cooling water.
When measured amounts of both reactants have been combined, the mixture is
held for a period of time to ensure completion of the reaction. A nonreactive
organic solvent is then used to extract the product from a mixture of methanol,
excess sodium methoxide, and byproduct sodium chloride. Suitable extraction
solvents are carbon tetrachloride, methylene dichloride, and diethyl ether. The
extraction solvent is decanted from the mixture, washed with water solutions of
sodium hydroxide, and fractionally vacuum-distilled to separate the extraction
solvent for recycle and to separate ronnel from side reaction byproducts.
Throughout this process, the temperature probably does not exceed 150° C. The
highest temperature probably occurs in the base of the final distillation column. In
theory, additional dioxins are not likely to be created by this process because of the
absence of high temperature and pressure, although all other conditions meet the
requirements for formation of 2,3,7,8-TCDD (see Figure 15, p. 61).
It appears even less likely that dioxins originally present in the Na-2,4,5-TCP
raw material would be carried through into the product. If all the steps outlined
above are properly conducted, some of the operations might isolate dioxins into
waste streams. The solubility of dioxins in thiophosphoryl chloride is unknown; if
they are insoluble, they would be removed with the first filtration. Because the
solubility of dioxins in chlorinated methanes is very slight (0.37 g/liter for TCDD
in chloroform), much of the dioxin present would not be captured by the extraction
solvent and would be carried away with the methanol reaction solvent.
Distillations afford two other opportunities to isolate dioxin contaminants into
waste organic fractions. Although the probability of dioxins carrying through into
the final product appears slight, definitive information is not recorded.
105
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Ronnel is reportedly produced by only one company—Dow Chemical
Company, Midland, Michigan (Stanford Research Institute 1978). Annual
production volume is not known. It is found in over 300 pesticide formulations
registered by more than 100 companies.
Chlorophenol Derivatives with Unconfirmed Dioxin Content
This subsection deals with several other chlorophenol derivatives that may
contain dioxins. The compounds discussed include those that have been analyzed
for dioxin content with negative results and also those for which analytical data
have not been reported.
Hexachlorophene—
Hexachlorophene is known chemically as either bis-(3,4,6-trichloro-2-
hydroxyphenyl) methane, or 2,2'-methylene-bis (3,4,6-trichlorophenol). It is also
known commercially as G-l 1 (Cosmetic, Toiletry, and Fragrance Association, Inc.
1977). Hexachlorophene is an effective bactericide and fungicide. Prior to 1972 it
was widely advertised and distributed as an active constituent of popular skin
cleansers, soaps, shampoos, deodorants, creams, and toothpastes (Wade 1971;
U.S. Dept. HEW 1978). Although its use has been considerably restricted by the
Food and Drug Administration, it still may be used as a preservative for cosmetics
and over-the-counter drugs; the concentration is restricted to 0.1 percent in these
products. Skin cleansers containing higher levels may also be sold but only as
ethical Pharmaceuticals, available by medical prescriptions (U.S. Code of Federal
Regulations Title 21 1978). As an agricultural pesticide, hexachlorophene is a
constituent of formulations used on three vegetables and on some ornamental
plants for control of mildew and bacterial spot. It is also used in limited industrial
and household applications as a disinfectant.
The grade of hexachlorophene produced today is reported to contain less than
15 Mg/kg (< 15ppb)2,3,7,8-TCDD (World Health Organization 1977). In a 1972
analysis, dioxins could not be detected in hexachlorophene at a detection limit of
0.5 mg/kg (0.5 ppm) (Helling et al. 1973).
Four process patents have been issued on manufacture of hexachlorophene, and
all are variations of the following chemical reaction:
Cl Cl
2.O-TCP HEXACHLOROPHENE
Hexachlorophene is formed by reacting one molecule of formaldehyde with two
molecules of 2,4,5-TCP at elevated temperatures in the presence of an acid catalyst
(Moye 1972). The patented processes differ in temperature, reaction time, order of
reagent additions, reaction solvents, and other physical parameters.
In the first process, patented in 1941, methanol is the solvent and large amounts
of concentrated sulfuric acid are used to bind the water that is formed as a reaction
byproduct; the process takes place at 0° to 5° Covera24-hourperiod(U.S. Patent
Office 1941). A second patent issued in 1948 discloses that the methanol solvent is
106
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eliminated and the reaction is conducted with paraformaldehyde at an elevated
temperature (135° C) over a 30-minute period (U.S. Patent Office 1948). A 1957
patent reintroduces a solvent, which is one of several chlorinated hydrocarbons
(U.S. Patent Office 1957d). Temperature is 50° to 100° C, and reaction time is 2 to 3
hours. Oleum (sulfuric acid plus SOa) is used as the catalyst and concentrated
sulfuric acid is recovered as the byproduct. Finally, a 1971 patent revises the order
of reagent addition and also emphasizes the chemical reaction mechanism (U.S.
Patent Office 1971). This last-mentioned process is probably the one in present use;
its processing sequence is shown in Figure 32.
Patent information indicates that older manufacturing methods probably
reclaimed the product from the reaction mixture by neutralizing the sulfuric acid
with sodium hydroxide, which would have created a rather large amount of brine
waste. In modern processes, conditions are probably maintained so that the
residual sulfuric acid separates as a distinct liquid layer when agitation of the
mixture is stopped after completion of the reaction. This acid, which contains the
water formed during the reaction, is decanted from the mixture; it is strong enough
to be used elsewhere in the plant complex, although it probably cannot be used in
subsequent hexachlorophene batches.
In the patent examples, the organic layer that remains after the acid is removed is
mixed with activated carbon, which is then filtered from solution. The purpose of
this treatment is to remove colored impurities. The clear filtrate is then chilled to
approximately 0° C; crystals of hexachlorophene precipitate and are filtered from
solution, dried, and packaged. The filtrate, which would contain some
hexachlorophene, is probably directly recycled for use in succeeding batches.
There is no indication that dioxins would be formed during the production of
hexachlorophene, since highly acidic conditions are maintained throughout the
process and temperatures are well below those known to be needed for dioxin
reactions (Kimbrough 1974). If dioxins are found in hexachlorophene, the most
likely explanation for their presence is that contamination in the 2,4,5-TCP raw
material is carried through into the final product (see Figure 27, p.74). In a
situation identical to that of the 2,4,5-T process, the patent descriptions show the
possibility of activated carbon adsorption, which could cause accumulation of
dioxins into an extremely hazardous waste. If carbon adsorption is not used in
commercial practice or if it is not totally effective, any dioxins in the raw material
will either appear in the hexachlorophene product or be recycled to succeeding
batches. Although dioxins are not known to be soluble in sulfuric acid, they might
be carried out of the process with the acid byproduct; if this were the case, dioxins
could then appear in other products of the plant in which the sulfuric acid is
utilized.
Givaudan Corporation in Clifton, New Jersey, is apparently the only active U.S.
producer of hexachlorophene. Until 1976, the 2,4,5-TCP for hexachlorophene
manufacture was produced by Givaudan's ICMESA plant in Seveso, Italy, and
shipped to New Jersey for conversion. In 1976, Wright State University analyzed
two representative samples of this trichlorophenol and found 1.8 and 1.9 ppb
TCDD's (Tiernan 1976). An accident in 1976 closed the ICMESA plant and
eliminated Givaudan's primary supply of 2,4,5-TCP. (For further details of the
ICMESA incident see Section 5, p. 168). It is now believed that all the 2,4,5-TCP
for hexachlorophene manufacture is supplied by Dow Chemical Company and
that Givaudan specifies an extremely low dioxin content. In 1978, five waste
samples from the Clifton plant were analyzed for chlorinated dioxins. None were
found at a 0.1 ppm level of detection (U.S. Environmental Protection Agency
1978d). Subsequent analysis of three of these samples found no TCDD's at 0.1 or
less ppb (see Section 4 of this report).
About 400 commercial products containing hexachlorophene have been
marketed recently in pesticide, drug, cosmetic, and other germicidal formulations.
The annual production volume of the germicide is not reported.
107
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2,4,5-
Trichlorophenol
Chlorinated
Hydrocarbon
Sulfunc Acid
and SO „
Activated
Carbon
Figure 32. Flow chart for hexachlorophene manufacture.
108
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Bithionol—
Bithionol (2,2'-thio-bis[4,6-dichlorophenol]) is an antimicrobial agent that was
approved at one time for drug use by the U.S. Food and Drug Administration. This
approval was withdrawn in October 1967 because the chemical was found to
produce photosensitivity among users (Kimbrough 1974; Merck Index 1978). The
U.S. EPA continues to approve its use as a pesticide in three animal shampoo
formulations. These formulated bithionol products may no longer be actively
marketed, however, because the single basic source of this chemical (Sterling
Drug's Hilton-Davis Chemical Co.) apparently no longer produces it (Chem
Sources 1975; Stanford Research Institute 1978).
The manufacture of bithionol is a one-step reaction between 2,4-dichlorophenol
and sulfur dichloride (U.S. Patent Office 1962; U.S. Patent Office 1958b). Carbon
tetrachloride is used as the solvent, and a small amount of aluminum chloride
serves as the catalyst. Bithionol is formed in a reaction at about 50° C; batch time is
about 2 hours. The chemical reaction is shown below.
OH
CA^ .
SCI2 _
AICI3
BITHIONOL
Two methods of product recovery are outlined in one process/patent (U.S.
Patent Office 1958b). In one method, water is added and impure bithionol
precipitates. To form a crude product, it is necessary only to filter the solids from
the mixture and wash them several times in water and cold carbon tetrachloride.
They are then dried and packaged.
Alternatively, to recover a purified product, water is added and the mixture is
distilled to remove the carbon tetrachloride for recycle. Bithionol collects as an
organic sediment, which is separated from the water solution by decantation,
washed with water and sodium bicarbonate, vacuum-dried, redissolved in hot
chlorobenzene, filtered, chilled to precipitate bithionol, and again filtered.
A separate patent outlines a procedure for forming metallic salts of bithionol,
which are compounds that permanently impregnate cotton fabrics with
disinfectant properties (U.S. Patent Office 1962). The process uses sodium
hydroxide and various metallic salts in room-temperature reactions, with water as
the solvent.
This manufacturing dperation apparently provides no potential for production
of dioxins by the known process of dioxin formation. In the manufacture of crude
bithionol, there is no opportunity to reject any dioxins that may be present in the
2,4-dichlorophenol raw material. They would be carried through into the final
product.
If bithionol is purified by the process outlined above, one filtration operation
would remove compounds that are insoluble in hot chlorobenzene. Some dioxins,
however, are slightly soluble in this solvent and thus might persist even in purified
bithionol or its salts.
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Sesin—
Sesin is an ester based on 2,4-dichlorophenol. The manufacture is similar to that
of erbon, a 2,4,5-TCP-based herbicide described earlier. Although details of the
first process step have not been reported, general organic chemical references
indicate that sesin manufacture probably begins by a reaction between 2,4-
dichlorophenol and ethylene chlorohydrin, as shown in the reaction sequence that
follows (March 1968). Water is the most likely solvent, made strongly alkaline with
sodium hydroxide, and the intermediate probably precipitates on addition of acid
and is filtered from solution and dried.
OCH2CH2OH
CICH2CH2OH
NaOH
Cl
2,4-DICHLOROPHENOL
C02H
H2SO4
OCH2CH20-C—(' ^
SESIN
A process patent discloses that the second reaction step is a combination of the
intermediate with benzoic acid (U.S. Patent Office 1956d). Xylene is the solvent,
and a small amount of sulfuric acid is used to remove the water formed in the
reaction.
The resulting reaction mixture is neutralized with sodium carbonate and is then
fractionally distilled under vacuum to recover the xylene for recycle and possibly to
separate the product from any impurities.
The first step of the reaction is the one that could possibly form dioxins. Both the
raw material and the resulting intermediate contain a chlorine atom ortho to a ring-
connected oxygen atom, and the mixture is heated with sodium hydroxide. High
temperature is not present, however. Since water is probably the solvent, this
simple reaction would not ordinarily require application of pressure. Dioxin
formation could occur at the surface of steam coils if high-pressure steam is used
for distillation.
Apparently no operation other than the final distillation would remove any
dioxin contamination from this material. Even this distillation may not isolate
dioxins into a waste stream. Most dioxins either formed by the process or present in
the raw material would probably be collected with the final product.
110
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Triclofenol Piperazine—
A pharmaceutical compound can be made from commercial 2,4,5-
trichlorophenol for use as an anthelmintic (deworming medication) (U.S. Patent
Office 196 la; Short and Elslager 1962). The research and animal tests of this drug
were conducted prior to 1962 with unpurified commercial-grade 2,4,5-TCP. The
drug was made by dissolving the chlorophenol in warm benzene and adding a
measured quantity of piperazine. The resulting solution was filtered to remove
insoluble matter, diluted with petroleum ether, and chilled. Crystals of the drug
precipitated and were filtered from the mixture, washed with petroleum ether,
dried, and packaged in gelatin capsules.
If this drug is being manufactured, the volumes are very low because it is not
listed in most pharmaceutical trade references. Manufacture would probably be by
the same process used in the laboratory, probably in very small batches, and with
equipment not much larger than standard laboratory apparatus.
Any dioxins present in the TCP raw material are probably discharged in plant
wastes rather than being concentrated into the pharmaceutical. Most of the dioxin
probably is filtered from the benzene solution as part of the insoluble matter. Since
some dioxins are slightly soluble in both benzene and petroleum ether, a portion
might remain in solution and be transferred to solvent recovery distillation
columns. The remaining dioxin would be discarded as part of an anhydrous tar
from the base of these columns. The pharmaceutical industry usually incinerates
both solid organic residues and solvent recovery tars.
Dicamba—
The herbicide dicamba is a derivative of salicylic acid known chemically as 3,6-
dichloro-2-methoxybenzoic acid. In 1972, analysis of eight samples indicated no
tetra-, hexa-, or hepta-CDD's at a detection level of 0.5 ppm (Woolson, Thomas,
and Ensor 1972). The presence of DCDD's is theoretically possible, however (see
Figure 23, p. 70).
Dicamba is made by acylation of 3,6-dichlorosalicylic acid, which in turn is made
from 2,5-dichlorophenol. The chemical reactions are shown below.
OH
C'CH30S03CH3HO
NaOH
2,5-DICm.OROPHEHOl. DICAMBA
The first step is known as the Kolbe-Schmitt reaction and is also used to make
unsubstituted salicylic acid from unsubstituted phenol in addition to haloginated
derivatives (U.S. Patent Office 1955a). Operating temperature is probably below
200° C, and operating pressure is probably greater than 8 atmospheres. The
chlorinated salicylic acid is mixed into water and sodium hydroxide and treated
with dimethyl sulfate (U.S. Patent Office 1967a). The reaction is conducted initially
with refrigeration to retard the otherwise violent reaction; the mixture is then
heated for a few hours at reflux temperature (slightly above 100° C).
On completion of the reaction, the mixture is acidified with hydrochloric acid.
Dicamba precipitates and is filtered from the mixture, rinsed with water, and dried.
Recrystallization from an organic solvent such as ether is possible, but probably is
not conducted in commercial practice.
Except for high temperature, all conditions necessary for formation of
chlorinated dioxins are present. It is likely that at high temperature dicamba would
111
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lose carbon dioxide in a reversal of the initial manufacturing reaction, and any
dioxins formed would not contain carboxyl groups.
Dicamba is reported to be made by Velsicol Chemical Corporation in
Beaumont, Texas, under the trade name Banvel (Stanford Research institute
1978). It is commercially available in many formulated pesticide products.
Other Chlorophenot Derivatives—
Compounds other than the products listed above are also potential dioxin
sources, but are made and used in smaller volumes.
A compound with the trade name of Irgasan B5200 is used as a bactenostat and a
preservative. Often described by the generic abbreviation TCS, it is an acid amide
derivative of a chlorinated salicylic acid, made by first reacting 2,4-dichlorophenol
with sodium hydroxide and carbon dioxide at high pressure, then reacting the
resulting intermediate with 3,4-dichloroaniline (U.S. Patent Office 1955a).
The germicide Irgasan DP-300 is a predioxin that was once sold in this country
by Ciba-Geigy Corporation. As outlined in Section 2, it was used in some of the
research of chlorinated dioxin chemistry, and dioxins were formed readily on
heating of this compound. Its chemical formula is as follows:
CIHO
This compound is a derivative of 2,4-dichlorophenol, although the process of
manufacture has not been reported.
The formulation called Dowlap was once used in the Great Lakes to control the
sea lamprey, an eel-like fish. The active ingredient of the formulation was 3,4,6-
trichloro-2-nitrophenol, whose chemical formula is as follows:
Cl
Cl
This compound was made by direct nitration of 2,4,5-tnchlorophenol using
concentrated nitric acid in a solvent of glacial acetic acid (Merck Index 1978).
A dye assistant chemical for use with polyester fibers was once made with the
trade name Tyrene (Merck Index 1978). Its chemical name is 2,4,6-trichloroanisole
or 2,4,6-trichloromethoxybenzene, with a structural formula as follows:
Cl
0-CH3
It was probably made by acylation of 2,4,6-trichlorophenol with dimethyl sulfate.
112
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Dioxins in Chlorophenol Production Wastes
Although the dioxin content of many products containing chlorophenols or
their derivatives has been reported in the literature, little information is available
on dioxins in the industrial wastes created by chlorophenol manufacture. One
unpublished report (U.S. Environmental Protection Agency 1978d) describes
analysis for dioxins in 20 samples of liquid wastes from plants manufacturing
trichlorophenol, pentachlorophenol, and hexachlorophene. The limit of detection
was 0.1 ppm. No TCDD's were detected in any of the samples. Hexa-, hepta-, and
octachlorodioxins were found in the pentachlorophenol wastes. The report does
not indicate clearly whether any of the higher chlorodioxins were found in the
hexachlorophene wastes.
Considerations of solubility and volatility suggest that large concentrations of
dioxins will be found in the still bottom wastes from 2,4,5-TCP manufacture.
Direct analytical evidence to this effect, though limited, is affirmative. Waste oils
identified as early 1970 still residues from a former 2,4,5-TCP manufacturing plant
in Verona, Missouri, have been analyzed and reported to contain ppm quantities of
2,3,7,8-TCDD (Johnson 1971; Commoner and Scott 1976a). A toluene still bottom
waste taken from Transvaal's plant in Jacksonville, Arkansas, has recently been
found to contain 40 ppm of TCDD's (Watkins 1979; also see Section 4 of this
report).
The effect of biological treatment on removal of dioxins from liquid industrial
wastes is not known. In 1978, the Dow Chemical Company reported that no
2,3,7,8-TCDD could be detected in 13 of 14 grab and composite samples from the
secondary and tertiary outfall of its manufacturing plant, which produces large
quantities of 2,4,5-TCP, 2,4,5-T, and other chlorophenolic compounds; one
sample was questionable. The reported level of detection ranged from 1 to 8 ppt.
No information is given on the dioxin content of the untreated waste stream or on
the treatment methods.
Apparently it has been common practice for chemical manufacturers to dispose
of dioxin-contaminated wastes or other toxic chemical wastes by landfill. Either
liquid or solid forms of the wastes are placed in drums and stored or buried. Dioxin
wastes disposed of in this manner would be expected to be quite concentrated.
Recently ppt to ppb levels of TCDD's were reported in environmental samples
from two landfills in Niagara Falls, New York (Chemical Week 1979). Hooker
Chemical reportedly has dumped a total of 3700 tons of 2,4,5-trichlorophenol
wastes over the past 45 years in these two dumps (Hyde Park and Love Canal) and
in one other disposal site on the company's Niagara Falls property. The report
estimated that the wastes buried in these landfills could contain over 100 pounds of
TCDD's.
At the Transvaal pesticide plant in Jacksonville, Arkansas, more than 3000
barrels of dioxin-contaminated wastes are stored on the plant property (Fadiman
1979). The total quantity of TCDD present in the wastes has not been estimated.
No other known information describes the quantities of dioxins that might be
buried elsewhere in the United States. In an effort to identify areas where landfills
are most likely to contain large dioxin wastes, Figure 33 illustrates the locations
where chlorophenols and their derivatives are now or were formerly produced. A
list of these locations is presented in Table 19; note that this list does not include
locations of the many companies that are believed only to formulate or otherwise
merchandise the chlorophenols or their derivatives.
A detailed discussion of the methods used for disposal of dioxins is presented in
Section 8. Additional information related to the environmental effects of dioxin
disposal is presented in the subsection on Water Transport in Section 7.
HEXACHLOROBENZENE
In 1974, a technical paper reported the presence of OCDD in samples of
commercial hexachlorobenzene (Villaneuva et al. 1974). Three samples were
113
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1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11
12
13.
14.
15.
16.
Philadelphia, PA
San Mateo, CA
Portland, OR
Cleveland, OH
Midland, Ml
Tuscaloosa, AL
Linden, NJ
Clifton, NJ
Naperville, IL
Jacksonville, AR
Springfield, MO
Niagara Falls, NY
Dover, OH
Shenandoah, IA
Rahway, NJ
Whiteford, MD
17
18
19.
20.
21.
22.
23.
24.
25.
26
27
28.
29.
30.
31
Sauget, IL
Chicago, IL
Kansas City, KS
Verona, MO
Tacoma, WA
St. Paul, MN
St Joseph, MO
Chicago Heights, IL
Nitro, WV
Ambler, PA
Fremont, CA
Port Neches, TX
St. Louis, MO
Wichita, KS
Orlando, FL
Figure 33. Locations of current and former producers
of chlorophenols and their derivatives.
I14
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TABLE 19. LOCATIONS OF CURRENT AND FORMER PRODUCERS OF
CHLOROPHENOLS AND THEIR DERIVATIVES3
Producer
Location
Chemical Type
Alco Chemical Corp.
J. H. Baxter and Company
Chempar
Diamond Shamrock Corp.
Dow Chemical Company
Fallek-Lankro Corp.
GAF
Givaudan Corporation,
Chemicals Division
Guth Corp.
Hercules, lnc.b
Hoffman-Taft, Inc.
Hooker Chemical Corp.
Occidental Petroleum Corp.,
subsidiary
ICC Industries, Inc., Dover
Chemical Corp., subsidiary
Imperial, Inc.
Merck and Co , Inc.
Miller Chemicals,
Alco Steel subsidiary
Philadelphia, PA
San Mateo, CA
Portland, OR
Cleveland, OH
Midland, Ml
Tuscaloosa, AL
Linden, NJ
Clifton, NJ
Naperville, IL
Jacksonville, AR
Springfield, MO
Niagara Falls, NY
Dover, OH
Shenandoah, IA
Rahway, NJ
Whiteford, MD
2,4-D
PCP
2,4,5-T
2,4-D
2,4,5-TCP
2,4,5-T
2,4-D
2,4,5-TCP
2,4,6-TCP
2,3,4,6-Tetrachlorophenol
2,4-D
2,4,5-T
Silvex
Ronnel
Erbon
DMPA
2,4-D
2,4-D
Hexachlorophene
2,4-D
2,4-D
Silvex
2,4,5-TCP
2,4,5-T
2,4,5-TCP
PCP
2,4-D
2,4,5-TCP
2,4-D
(continued)
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TABLE 19. (continued)
Producer
Location
Chemical Type
Monsanto Company
Monsanto Industrial
Chemicals Company
Nalco Chemical Co.
Sauget, IL
Chicago, IL
North American Phillips Corp., Kansas City, KS
Thompson-Hayward Chemical
Co., subsidiary
North Eastern Pharmaceuticals Verona, MO
PBI-Gordon Corporation0 Kansas City, KS
Private Brands, lnc.c
Reichhold Chemicals, Inc.
Rhodia, Inc.
Agricultural Division
Riverdale Chemical Co.
Roberts Chemicals, Inc
Rorer-Amchem
Amchem Products, Inc ,
Divisiond
Sanford Chemicals
Thompson Chemicals
Kansas City, KS
Tacoma, WA
Portland, OR
St. Paul, MN
St. Joseph, MO
Chicago Heights, IL
Nitro, WV
Ambler, PA
Fremont, CA
St. Joseph, MO
Port Neches, TX
St. Louis, MO
Union Carbide Corp. Ambler, PA
Agricultural Products Division Fremont, CA
Amchem Products, Inc., St. Joseph, MO
subsidiary1*
Vertac, Inc
Transvaal, Inc.,
subsidiary11
Jacksonville, AR
PCP
2,4,5-T
2,4-D
PCP
2,4,5-TCP
2,4-D
2,4,5-T
Silvex
2,4,5-TCP
2,4-D
2,4,5-T
2,4-D
2,4,5-T
PCP
2,4-D
2,4-DB
2,4-D
2,4,5-T
Silvex
2,4,6-TCP
2,4,5-T
2,4-D
2,3,4,6-Tetrachlorophenol
PCP
2,4,5-T
2,4-D
2,4-D
2,4,5-T
2,4,5-TCP
2,4-D
2,4,5-T
Silvex
(continued)
116
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TABLE 19. (continued)
Producer Location Chemical Type
Vulcan Materials Co. Wichita, KS PCP
Chemicals Division
Woodbury Orlando, FL 2,4-D
Comutrix subsidiary
a—Sources Stanford Research Institute Directory of Chemical Producers, United States 1976,
1977, 1978, and 1979. U S. Tariff Commission. Synthetic Organic Chemicals, United States
Production and Sales 1968 U S. International Trade Commission Synthetic Organic Chem-
icals, United States Production and Sales 1974, 1976, 1977, and 1978
b—Hercules, Inc , was a former owner of the Jacksonville, AR, facility now owned by Vertac, Inc
c—Private Brands, Inc., is believed to be a former owner of the Kansas City, KS, facility now owned
by FBI-Gordon Corp
d—Former Rorer-Amchem facilities in Ambler, PA, Fremont, CA; and St Joseph, MO, are now
owned by Union Carbide Corp
analyzed, two of which contained OCDD in concentrations of 0.05 and 211.9ppm.
All three contained octachlorodibenzofuran (OCDF) in concentrations of 0.34,
2.33, and 58.3 ppm. One sample contained a trace amount of
heptachlorodibenzofuran. It was established that the principal impurity in these
samples was pentachlorobenzene in amounts ranging from 0.02 percent to 8.1
percent. When the samples were examined qualitatively, 11 other impurities having
polychlorinated ring-type structures were identified:
Octachlorobiphenyl
Decachlorobiphenyl
l-Pentachlorophenyl-l,2,3-dichloroethylene
Decachlorobiphenyl
Octachlorobiphenylene
Octachloro-l,l-bicyclopentadienylidene
Hexachlorocyclopentadiene
Nonachlorobiphenyl
Decachlorobiphenyl
Pentachloroiodobenzene
Heptachloropilium
It is significant that this list includes no phenolic compounds and no predioxins or
isopredioxins. In fact, the only compounds in these samples that contain oxygen
are dioxins and dibenzofurans.
Uses
Hexachlorobenzene is a registered pesticide formerly used to control a fungus
infection of wheat. It is also a waste byproduct from manufacturing plants that
produce chlorinated hydrocarbon solvents and pesticides (Villaneuva 1974; U.S.
Environmental Protection Agency 1978g). It can be used as a raw material in the
manufacture of pentachlorophenol, but is not so used in this country.
Hexachlorobenzene is not the same compound as benzene hexachloride. The
empiric formula of hexachlorobenzene (HCB) is C6C16, and its structure is that of
benzene in which all of the hydrogen atoms have been replaced with chlorine.
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Benzene hexachloride (BHC) is the common name of hexachlorocyclohexane. Its
empiric formula is C6H6C16, and its structure results from direct addition of
chlorine to benzene rather than from replacement of hydrogen. One stereoisomer
of BHC, the gamma form, is a powerful insecticide, and its use in this country is
severely restricted. It is still made, however, because BHC is an intermediate in the
most common synthesis method of producing HCB.
Manufacture
In the manufacture of HCB, the first step is a photochlorination, in which
chlorine gas is bubbled through benzene (Wertheim 1939; U.S. Patent Office
1955b). This occurs in a specialized reaction vessel fitted with a strong source of
ultraviolet light. In a low-temperature reaction, the light catalyzes the conversion
of approximately 25 percent of the benzene into a mixture of BHC isomers. This
mixture is "crude" BHC, consisting of about 65 percent of the alpha isomer, 10
percent beta, 13 percent gamma, 8 percent delta, and 4 percent epsilon. It is
separated by distilling off most of the excess benzene for recycle and then filtering
the BHC crystals from the mixture.
All stereoisomers of BHC are equally suitable for the manufacture of HCB. The
continuation of the process consists of mixing BHC with chlorosulfonic acid or
sulfuryl chloride and holding the mixture at approximately 200° C for several
hours (U.S. Patent Office 1957a). This step removes the hydrogen from BHC and
thereby restores the unsaturated benzene ring. When the mixture is cooled, HCB
precipitates and is separated by filtration, rinsed with water, dried, and packaged.
The following shows the overall chemical reactions of the process.
Cl H
+ CL
U.V. LIGHT
BENZENE
H Cl
BHC
CISO3H
+ HCI
+ H2O
+ SO,
HEXACHLOROBENZENE
Descriptions of these process steps provide no indication that dioxins are
formed. The raw materials are benzene, chlorine, and chlorosulfonic acid, none of
118
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which are likely sources of dioxins. The only reactant that could contribute the
oxygen needed to complete the dioxin ring is chlorosulfonic acid, but in this
compound the oxygen is tightly bound in a linkage with sulfur.
There is, however, a supplemental process that contributes other chemicals that
may lead to dioxin formation. This extra step may be conducted at some plants, or
may have been conducted in earlier years. If a market exists forthe sale of gamma-
BHC as an insecticide, this material is extracted from the mixture of crude BHC
and benzene after most of the excess benzene has been distilled off for recycle. To
this concentrated solution, water is added, along with other chemicals. The
objective is to form an emulsion that will entrain part of the BHC. The solution is
then filtered; the emulsion passes through the filter, while the solids that were not
emulsified are captured. Since gamma-BHC accumulates preferentially in the
emulsion, the solids from this first filtration are used for HCB manufacture and the
filtrate is treated with salt to break the emulsion and then refiltered. The second
crop of solids contains up to three times as much gamma-BHC as the crude product
and is dried and sold separately (U.S. Patent Office 1955b).
As indicated by the process patent, chemicals added during this supplemental
step include a wide range of organic detergents and solvents, but none of those
listed are phenolic or have been shown to create dioxins. Detergents of the anionic
type are preferred, especially salts of sulfonated succinic esters, although any of the
common surface-active agents are suitable. Supplemental solvents may not be
employed, since benzene alone is said to be preferred, but other suitable solvents
include dioxanes, any of the aliphatic substituted benzenes, any of the common
chlorinated paraffin hydrocarbons, kerosenes, and ethyl ether. Dioxane is the one
compound listed that might contribute to dioxin formation, although the reaction
is not reported in published literature.
Production
Current information on the volume or production of hexachlorobenzene is
uncertain. Annual production estimates range from 420,000 to 700,000 pounds.
Stauffer was the only reported domestic producer in 1974; Dover Chemical
Company of Niagara Falls, New York, was the only reported producer in 1977
(U.S. Environmental Protection Agency 1978g). Dioxins have not been reported in
any other chlorobenzene compounds.
OTHER PHENOLIC COMPOUNDS WITH DIOXIN-FORMING
POTENTIAL
Several compounds with a phenol nucleus that do not contain chlorine are now
being manufactured or were manufactured at one time. Four such compounds or
classes of compounds are examined for their dioxin-forming potential in this
section. (See also Table 7, page 38)
Brominated Phenols
Three brominated phenolic compounds were once manufactured, and may still
be. Because brominated dioxins have been made in laboratory experiments, they
may be created during the manufacture of these compounds.
Published data describe the production method fortetra-bromo-cresol, which is
made by direct bromination of o-cresol in a solvent of carbon tetrachloride with
aluminum and iron powders as catalysts (U.S. Patent Office 1943). The following
reaction is conducted at room temperature, and it requires about 24 hours to
complete a batch.
119
-------
Br-
0-CRESOL
TETRABROMO-0-CRESOL
When the reaction is complete, the mixture is heated to about 80° C to drive off the
carbon tetrachloride solvent and excess bromine. The residue is mixed with dilute
hydrochloric acid to form a slurry, which is then filtered. The resulting solids are
washed with water, dried, and packaged. Yield is about 95 percent.
It is possible to recrystallize this product to separate nonphenolic impurities by
dissolving the crude product in sodium hydroxide solution, filtering out insolubles,
neutralizing the mixture with hydrochloric acid, and refiltenng. This step may or
may not be conducted in commercial practice.
Two other brominated phenolic compounds are believed to be made by
essentially the same process. Structural formulas are as follows:
Br
2,4,6-TRIBROMOPHENOL
2,4,6-TRIBROMO-M-CRESOL
Almost all brominations of organic compounds are low-temperature processes
because bromine is readily vapori/.ed and would be driven from the reaction vessels
at high temperatures. A metallic catalyst is needed to activate the diatomic liquid
bromine, and a volatile solvent is usually employed to maintain all reactants in the
liquid state.
Because the temperature during manufacture of these compounds does not
usually exceed 80° C except at the surface of heating coils, dioxin formation would
not be expected. If dioxin contamination enters with the raw materials, brominated
dioxins likely would appear in the crude product. If the product is recrystalhzed,
the dioxins could be constituents of a waste sludge.
The literature mentions dioxins that are both brominated and methylated (see
Table 5). By the known process of dioxin formation, 2,4,6-tribromo-m-cresol
would be expected to form several dimethyltetrabromodioxins, and other cresols
would also, in theory, form dimethyl dioxins.
O-Nitrophenol
There is no direct utilization of o-nitrophenol as a completed chemical. It is a
chemical synthesis intermediate, although it has fewer uses than /?-nitrophenol.
120
-------
The manufacture of o-nitrophenol is a hydrolysis of o-nitrochlorobenzene with
sodium hydroxide in a process essentially identical to the hydrolysis method of
chlorophenol production. The chemical reaction is as follows:
+ NaCI
Although the operating conditions of this reaction are not known, conditions of
temperature are probably mild. In nitrochlorobenzenes, the chlorine atom is
weakly attached, especially when the substituents are in the ortho position. The
chlorine atom behaves like that of an alkyl halide and is readily replaced. In
contrast, the nitro group is very strongly attached and its replacement is difficult
(Wertheim 1939).
Unsubstituted dioxin would be created if a further reaction did occur to remove
the nitrate group by the following theoretical reaction:
2NaN0
This reaction is possible, and o-nitrophenol may be a source of dioxin
contamination.
This compound is manufactured by the Monsanto Company, Sauget, Illinois.
Salicylic Acid
Salicylic acid is an important chemical synthesis intermediate used to make dyes,
flavoring chemicals, and pharmaceutical compounds such as aspirin.
Unsubstituted dioxin may be present, but has not been reported. Salicylic acid is
made by a high-pressure reaction between phenol and carbon dioxide in the
presence of sodium hydroxide; this reaction is known as the Kolbe-Schmitt
reaction.
CO2
NaOH
COOH
Operating temperature is about 150° C. Higher temperatures are avoided to
prevent a side reaction that forms p-hydroxybenzoic acid.
This process includes some of the conditions needed to produce Unsubstituted
dioxin, but not all of them. The hypothesis of possible dioxin formation is
strengthened, however, by observations of products created by thermal
decomposition of salicylic acid. When heated strongly, it decomposes primarily
121
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into phenol and carbon dioxide, but also into smaller amounts of phenyl salicylate,
which in turn condenses to xanthone:
PHENYL SALICYLATE
XANTHONE
Since the ortho carbon is held weakly in the salicylic acid molecule, and since the
triple-ring xanthone structure has been identified, the formation of dioxins may
also be possible, especially if oxygen is present.
Both salicylic acid and xanthone are widely distributed in nature. Salicylic esters
are responsible for some plant fragrances, and xanthone is a yellow pigment in
flowers.
Salicylic acid is manufactured by four companies in this country:
Dow Chemical Company—Midland, Michigan
Monsanto Company—St. Louis, Missouri
Hilton-Davis Chemical Company—Cincinnati, Ohio
Tenneco Chemicals, Inc.—Garfield, New Jersey
The combined capacity of these four plants is 24 million kilograms annually.
Aminophenols
The o-aminophenols could conceivably form dioxins through condensation with
loss of ammonia. These are not high-volume chemicals and are not known to be
made with halogen substituents. A class of related compounds is used in much
larger quantity; these are the derivatives of o-anisidine (methoxyaminobenzene),
which in several forms are important dye intermediate chemicals. These might
condense in appropriate environments into the dioxin structure through loss of
methylamine. The environments would probably be acidic:
O-CH3
2 NH2CH3
Although this reaction is possible, it is unlikely because the amine group is tightly
bound to the benzene ring. Aminophenols or similar compounds are not likely
sources of dioxin contamination.
DIOXINS IN PARTICULATE AIR EMISSIONS
FROM COMBUSTION SOURCES
Recent reports by chemists at the Dow Chemical Company maintain that dioxin
formation is a natural consequence of combustion (Dow 1978). There are
122
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numerous naturally occurring compounds that could, during the complex process
of combustion, serve as precursors of dioxins. Combustion of these compounds in
the presence of chlorine-containing compounds (e.g., DDT or polyvinyl chloride)
could lead to the formation of chlorinated dioxins. Examples of such naturally
occurring "potential" dioxin precursors are given below.
OH
I
CH3NHCH2CH
OH
OH
24
ADRENALINE
(EPINEPHRINE)
Catechol (22) occurs in nature as the product of phenol biodegradation and as a
major product of tannin pyrolysis (Wertheim 1939). Guaiacol (23) occurs as the
major phenolic component in several hardwood trees and is also prepared
synthetically for use as an ingredient in cough syrups (Merck 1978; U.S. EPA Draft
1979). Adrenaline (24) is a naturally occurring mammalian hormone and is also
prepared synthetically for use in many drug formulations (U.S. EPA Draft 1979).
Other naturally occurring compounds that contain the orthohydroxy or alkoxy
groups include vanillin (25), which is the flavoring ingredient in vanilla extract;
urushiol (26), a mixture of compounds that are the toxic constituents of poison ivy;
eugenol (27), the pungent principle of cloves; capsaicin (28) the pungent principle
of various peppers; and safrole (29), the major volatile constituent of sassafras.
CHO
OCH3
OH
26
R = C15H31
= C15H29
OCH3
= C15H25
= C15H23
URUSHIOL
CH2NHC-(CH2)£-CH=CHCH(CH3)2
28
CAPSAICIN
OCH3
CH2CH=CH2
27
EUGENOL
CH2CH=CH2
29
SAFROLE
123
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Among many plant alkaloids that include the structure are reserpine (30), glaucine
(31), and colchicine (32). Other potential dioxin precursors are found in the
fomecin (33) series of antibiotics, produced by a fungus, and also in one of the
active ingredients of creosote.
A constituent of animal urine is 4-hydroxy-3-methoxymandelic acid (Merck
Index 1978). Since the structure is so common in living organisms, it is also often
used in synthetic medicinal compounds, including phenisonone, isoproterenol,
estil (an anaesthetic), methocarbanol, and the high-volume drugs guaifenesin and
methyldopa (U.S. Environmental Protection Agency 1979).
OCH,
OCH,
CH30
CH30
30
RESERPINE
CHO
NHCOCH,
HOH2C
OCH3
32 3
COUHICIHE
33
FOMECIN
At least one natural compound may be by itself a precursor for a chlorinated
dioxin. A microorganism species creates a defensive chemical known as
drosophyllin A (34), (p-methoxytetrachlorophenol) (Merck Index 1978). In theory
it could, when heated, form a substituted hydroxy or methoxy chlorinated dioxin,
one possibility of which is:
+ 2HCI
34
DROSOPHVLLIN A
124
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Several reports describe the occurrence of dioxins in fly ash and flue gases from
municipal incinerators and industrial heating facilities. In 1977, analysis of samples
of fly ash from three municipal incinerators in the Netherlands showed 17 different
dioxins (5 TCDD's, 5 penta-CDD's, 4 hexa-CDD's, 2 hepta-CDD's, and OCDD)
(Olie, Vermeulen, and Hutzinger 1977). Although the specific number of isomers
was not stated, the same dioxins were found in flue gas from one of the incinerators.
In addition, large amounts of di-, tri-, and tetrachlorophenols were found in flue
gases, and high levels of chlorobenzenes, especially hexachlorobenzene, were
detected in all fly ash samples.
Another team of investigators reported finding the same dioxins in Switzerland
(Buser and Bosshardt 1978). This study quantitatively determined that the total
amount of polychlorinated dibenzo-p-dioxins in the fly ash from a Swiss municipal
incinerator and industrial heating facility were 0.2 ppm and 0.6 ppm, respectively.
High-resolution gas chromatography was then used to identify 33 specific dioxin
isomers found in the fly ash samples. The dioxin isomers known to be most toxic,
which are 2,3,7,8-TCDD, 1,2,3,7,8-penta-CDD, 1,2,3,6,7,8- and 1,2,3,7,8,9-hexa-
CDD, were only minor constituents of the total dioxins found.
Later in 1978, researchers at Dow Chemical Company reported finding ppb
levels of chlorinated dioxins in paniculate matter from air emissions of two
industrial refuse incinerators, a fossil-fueled powerhouse, and other combustion
sources such as gasoline and diesel autos and trucks, two fireplaces, a charcoal grill,
and cigarettes. (See Table 20.) All of these sources are believed to be located on or
near the Dow facilities in Midland, Michigan. Tetra-, hexa-, hepta-, and
octachlorodioxins were found. Concentrations of 2,3,7,8-TCDD were minor
relative to concentrations of other dioxins. Dow concluded from the study that
their Midland facility was not a measurable source of the dioxins found in fish from
nearby rivers, and that, in fact, chlorinated dibenzo-p-dioxins may be ubiquitous in
combustion processes. A preliminary data analysis by the EPA does not entirely
agree with Dow's conclusions. The EPA continues to believe that Dow's Midland
plant is the major and possibly the only source of the dioxins contaminating fish in
nearby rivers. The EPA has asked Dow for further clarification of the company's
findings and analytical methods (Merenda 1979).
In contrast to the Dow finding of 38 ppb TCDD's in powerhouse emissions,
Kimble and Gross (1980) report finding no TCDD's in fly ash from a typical
commercial coal-fired power plant in California; the detection limit was 1.2 ppt.
Crummett of Dow Chemical Company asserts that these studies could not have
found 2,3,7,8-TCDD to be present because the solvents used for the extraction
techniques in preparation for the analytical analysis were not appropriate.
In 1980 Wright State University chemists analyzed emissions from a U.S.
municipal incinerator for chlorodioxins (Tiernan and Taylor 1980). TCDD's were
detected in all seven samples. Isomer-specific analyses indicate that 2,3,7,8-TCDD
is a minor product, and evidence was obtained for the presence of 1,3,6,8-, 1,3,7,9-,
1,3,7,8-, 1,3,6,7-, and at least six other TCDD isomers.
The formation of dioxins from the thermal decomposition of chlorophenols
and their salts (chlorophenates) is well documented. In 1971, Milne reported
finding no evidence of formation of lower chlorinated dioxins from the thermal
decomposition of dichlorophenols; all six dichlorophenol isomers were studied.
However, Aniline (1973) found that pyrolysis of 2,3,4,6-tetrachlorophenate
produced two hexa-CDD isomers. Later, Stehl et al. (1973) found that burning
paper treated with sodium pentachlorophenate produced OCDD, but burning
either wood or paper treated with pentachlorophenol did not produce the dioxin.
In 1975, a series of pyrolysis experiments was conducted with 2,3,4-, 2,3,5-, 2,4,5-
and 2,3,6-tri, 2,3,4,5-, 2,3,5,6- and 2,3,4,6-tetra, and pentachlorophenates to obtain
samples of many tetra-, penta-, hexa-, and octa-CDD's for study (Buser 1975). In
1977, 2,3,7,8-TCDD was found as a combustion product of many 2,4,5-trichloro-
phenoxy compounds, but the amount of this dioxin was very small relative to the
125
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NJ
O
TABLE 20. DIOXINS IN SELECTED SAMPLES3
(ppb except as noted)
Source
Soil inside plant
Dust samples from Dow
Research Building
Soil and dust from
Midland and metro areas
Soil and dust from
major metro area
Soil and dust from
urban area
Soil and dust from
rural area
Dow stationary tar
incinerator particulates
Dow rotary kiln incinerator
TCDD's
Other
2,3.7,8-TCDD TCDD isomers Hexa-CDD's
0.3-100 0.8-18 7-280
0.7-2.6 0.5-2.3 9-35
0.03-0.04 0 09-0.4
0.005-0.03 0.02-0.14
none none 0.03-1 .2
none none none
none none 1-20
none none 1.4-5.0
Hepta-CDD's
70-3200
140-1200
0.3-3.9
0.10-3.3
0.035-1.6
0 02-0.05
27-160
4-110
OCDD
490-20,500
650-7500
04-31
0.35-22
0.05-2 0
0.10-0.35
1 90-440
9-950
with supplementary fuel
(continued)
-------
TABLE 20. (continued)
TCDD's
Source
Dow rotary kiln incinerator
without supplementary fuel
Dow powerhouse fired with
fuel oil/coal
Automobiles
catalytic - carbon
catalytic - rust
noncatalytic
diesel trucks
Fireplaces (scrapings)
Cigarettes (tars)
Charcoal-grilled steaks
Residential electrostatic
2,3,7,8-TCDD
110-8200
none
none
0.4
none
30
01
none
none
06
Other
TCDD isomers
1800-12,000
38
0.1
40
4.0
20.0
0.27
none
none
040
Hexa-CDD's
1 300-65,000
2
0.5-2.0
0.7
none
4-37
0.23-3.4
4.2-8.0
none
34
Hepta-CDD's
2000-510,000
4
2-14
3
3
35-110
0.67-16
8.5-9 0
3-7
430
OCDD
3000-810,000
24
8-72
28
10-16
1 90-280
0.89-25
18-50
5-29
1300
precipitator
Particulates from rotary kiln
scrubber water with
supplemental fuel
without supplemental fuel
(continued)
46
2500
200
3400
970
26,000
1200
42,000
-------
TABLE 20. (continued)
TCDD's
Other
Source 2,3,7,8-TCDD TCDD isomers Hexa-CDD's Hepta-CDD's
Filtered scrubber water 00028 0.005 0.024
Cooling tower residues 1.6-6.0 10 12-25
Sewer waters before treatment 1-4 N A.b NAb
(concentration - ppt)
OCDD
0026
56-119
3-1500
a—Source Dow Chemical Company 1978
b—N A = not applicable
-------
amount of the 2,4,5-trichlorophenoxy compound that was burned (Stehl and
Lamparski 1977). Results of the study showed that only 1.2 x 10-5 to 5 x 1(H
percent by weight of the 2,4,5-trichlorophenoxy species was converted to 2,3,7,8-
TCDD by combustion.
The origin of the dioxins in airborne particulates from combustion is not yet
clarified. Rappe et al. (1978) suggest that polychlorinated dibenzo-p-dioxins can be
formed during combustion by dimerization of chlorophenates, by dechlorination
of more chlorinated polychlorinated dibenzo-p-dioxins, and by cyclization of
predioxins. Dow Chemical Company (1978) suggests that because of the complex
nature of the materials being burned and the complex chemistries of fire, the
formation of chlorinated dioxins occurs in all combustion processes, i.e., that the
formation is not necessarily limited to combustion in the presence of
chlorophenates or chlorophenols. The presence of biosynthesized compounds with
characteristics of dioxin precursors may give some credence to this contention.
An alternative explanation for the observed presence of dioxins in the fly ash of
refuse incinerators is that the dioxins enter intact as contaminants of the wastes
being burned. For example, silvex-treated grass clippings, sawdust or other wastes
from PCP-treated wood (landscape timber, railroad ties), and "empty" PCP,
silvex, or other pesticide containers from home or industrial use might be direct
sources of the dioxins detected in municipal incinerator fly ash. If this were the
case, seasonal variations in fly ash dioxin content would be expected, with larger
amounts in spring and summer.
DIOXINS IN PLASTIC
In 1965, it was reported that dioxin is an impurity in the preparation of
polyphenylene ethers (Cox, Wright, and Wright 1965). No reports further
substantiating this finding are known. "PPO"is a trademark of General Electric
Company for a polyphenylene thermoplastic derived from 2,6-dimethylphenol
(Hawley 1971). The dioxin configuration one would expect from condensation of
the dimethylphenol is as follows:
OH
2 CH4
2,6-DIMETHYLPHENOL 1,6-DIMETHYLDIDENZO-P-DIOXIN
Because PPO is highly resistant to acids, bases, detergents, and hydrolysis, it
may be used in hospital and laboratory equipment, and in pump housings,
impellers, pipes, valves, and fittings in the chemical and food industries.
DIOXINS PRODUCED FOR RESEARCH PURPOSES
Many investigators have reported the sources of purified dioxin standards used
in their studies. Some of these dioxin sources and the names of the dioxins provided
are listed in Table 21.
In addition to these, Dow Chemical Company has recently published methods
for preparing all of the TCDD isomers (Nestrick, Lamparski, and Stehl 1979).
129
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TABLE 21. SOURCES OF PURIFIED DIOXIN SAMPLES FOR RESEARCH
Source
Dioxin provided
Reference
Givaudan Ltd.
Dubendorf, Switzerland
Dr. K Anderson
University of Umea,
Sweden
Dr. C. A. Nilsson
University of Umea,
Sweden
Stickstoffwerke
Linz, Austria
Dr. David Firestone
Food and Drug
Administration
Washington, DC, U S.A.
Dow Chemical Company
Midland, Ml, U.S.A.
ITT Research Institute
Chicago, IL, U.S.A
A. E Pohland
Food and Drug
Administration
Washington, DC, U.S.A.
A. Poland
McArdle Laboratory
for Cancer Research
University of Wisconsin
Madison, Wl, U.S.A.
Dow Chemical Company
Midland, Ml, U.S.A.
2-mono-CDD
2,3-di-CDD
2,7-di-CDD
2,8-di-CDD
1,2,4-tn-CDD
1,3,7-tn-CDD
2,3,7-tn-CDD
1,2,3,4-tetra-CDD
1,2,3,8-tetra-CDD
1,2,3,7-tetra-CDD
2,3,7,8-tetra-CDD
1,2,3,7,8-penta-CDD
1,2,4,7,8-penta-CDD
1,2,3,6,7,8-hexa-CDD
1,2,3,7,8,9-hexa-CDD
Unspecified dioxin
standards
1,2,4,6,7,9-hexa-CDD
1,2,3,6,7,9-hexa-CDD
1,2,3,6,7,8-hexa-CDD
1,2,3,7,8,9-hexa-CDD
1,2,3,4,6,7,9-hepta-CDD
1,2,3,4,6,7,8-hepta-CDD
2,3,7,8-TCDD
OCDD
"C-TCDD
Buser (1978)
Buser(1978)
Buser (1978)
Buser (1978)
Buser (1978)
Villanueva (1973)
Firestone (1977)
Firestone (1977)
O'Keefe et al. (1978)
hexa-CDD
hepta-CDD
octa-CDD
C. D. Pfeiffer(1978)
130
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SUMMARY
In summary, dioxins can enter the environment in a variety of ways:
1. As contaminants in commercial chemical products whose normal processing
conditions generate the dioxins as byproducts. Previous subsections detail the
mechanisms by which this can occur in some of these commercial chemicals.
2. As contaminants in chemical processing under improperly controlled reaction
conditions (Rappe 1978). Thus, dioxins would be present in the wastes from
"bad batches." Chemical manufacture that might lead to dioxin presence
under such circumstances is also reviewed above.
3. As products of intentional dioxin preparations in the laboratory. Although
the quantities involved from such sources probably would not be large, the
concentrations would be high. Therefore any failure to practice proper
disposal could be serious because of the high toxicity and concentration
potential. Reported laboratory dioxin preparations are noted in Section 2.
4. As deliberate or unintentional products of reactions carried out by
uninformed or irresponsible persons. The hazards in such cases would be
enhanced because the dioxins formed would likely be subject to improper use
or disposal.
5. As products of combustion of general municipal, commercial, and industrial
wastes. Such wastes are likely to contain materials required for dioxin
formation. The chlorine content of municipal waste is relatively high because
of the widespread use of polyvinyl chloride and other chlorinated polymers.
6. As combustion products and residues from burning vegetation that has been
sprayed with chlorinated herbicides (and other pesticides). This potential
source is of two-fold interest. First, chemicals such as 2,4,5-T, 2,4-D, and
others noted in this section might be degraded to dioxins under relatively mild
combustion conditions (Buu-Hoi 1971). Second, formation of dioxins might
occur under combustion conditions, even from chemicals not directly related
to dioxins, such as many insecticides (DDT, aldrin, dieldrin, etc.).
7. As incidental products of fires in facilities such as chemical and pesticide
warehouses, farm buildings in which pesticides are stored, and facilities for
storage of chemically treated wood products such as lumber or poles (Buu-Hoi
1971).
8. As waste disposal byproducts of materials such as polychlorinated biphenyls
(PCB's). These materials have been used extensively in electrical transformers,
as heat transfer media, as lubricants, and in carbonless paper.
9. As derivative wastes from pentachlorophenol (PCP) and other wood-treating
agents. Agents used in the treatment of wood products are likely to remain
with the wood through its use cycle. Thus they are subjected to the same
extremes of exposure as the wood, including ultimately combustion, which
leads to dioxin formation (Buu-Hoi 1971).
10. As an unsuspected byproduct of the treatment of aromatic compounds under
oxidizing conditions at elevated temperature. Several industrial processes
involve the oxidation of benzene, toluene, and naphthalene under
"semicombustion" conditions. In light of such studies as that by Dow
Chemical Company (Rawls 1979) on combustion sources of dioxins, the
"tars" from these processes (often occurring in considerable quantities)
warrant further study.
11. As byproducts of miscellaneous chemical syntheses that may not be
commercially significant at this time. An example might be the detected
presence of 2,3,7,8-TCDD in chlorinated polyphenylene ethers (such as 21),
which can be produced from 2,4,5-trichlorophenol (Cox 1965).
131
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OH
Cl
NaOH
Cl
Cl
These polymers are not known to be of commercial significance, but serve as a
cautionary example.
12. As a result of the combustion of naturally occurring compounds.
132
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SECTION 4
ANALYTICAL METHOD FOR DIOXINS
IN INDUSTRIAL WASTES
INTRODUCTION
Most of the current technology for detection of TCDD's is based on gas
chromatography and/or mass spectrometry. However, a variety of other less
specific techniques have been used, including ultraviolet spectroscopy (Pohland
and Yang 1972), electron spin resonance spectroscopy, and low-temperature
phosphorescence emission spectroscopy (Baughman 1974). None of these methods
provide both the high sensitivity and selectivity needed for analysis of most
environmental samples.
A resin sorption technique using X AD-2 resin has achieved a detection limit of 1
ppt for TCDD's in water; because this technique required a large quantity of
sample for extraction, however, extension to other types of samples is unlikely
(Junk 1976).
Another technique uses PX21 powdered charcoal suspended on shredded
polyurethane foam as the sorbant (Huckins, Stalling, and Smith 1978). The
TCDD's were eluted from the charcoal column by use of a 50 percent solution of
toluene in benzene and finally were detected by electron-capture gas
chromatography. To enhance selectivity, an alumina column chromatography step
is usually included after elution from the charcoal column. The detection limit of
this method ranges from 10 to 100 ppb.
Thin-layer chromatography has also been used for the detection of TCDD's
(Williams and Blanchfield 1971). Two-dimensional development with two
different solvents is used to increase selectivity. The spot corresponding to 2,3,7,8-
TCDD is removed from the plate, extracted with benzene, and detected by
electron-capture gas chromatography. This method has achieved a detection limit
in the low ppm region.
Steam distillation has also been tried (Storherr 1971), but was suitable only for
levels of TCDD's in the range of 1 to 3 ppm and lacked the selectivity needed to
avoid interferences.
Recently, analytical methods involving chemical ionization mass spectrometry
with negative ions have been published. An early communication by Hunt and co-
workers (Hunt, Harvey, and Russel 1975) reported a signal-to-noise ratio of 50
from a 2-pg direct-probe insertion sample using oxygen as the reagent gas. A
sensitivity 25 times higher than the direct-probe insertion method is reported for
electron impact ionization. Hass et al. compare the relative sensitivities of various
chemical ionization modes, including those of positive-ion versus negative-ion
modes with methane, oxygen, and mixed methane/oxygen as reagent gases (Hass
1978). Positive-ion chemical ionization affords the greater sensitivity, but does not
produce ions indicative of the molecular weight.
Since 1972 the personnel of the Brehm Laboratory of Wright State University
have been performing sensitive dioxin analyses under programs supported by
several agencies. In these investigations Brehm Laboratory has developed and
applied analytical methodology for the determination of TC DD's in many types of
samples, including herbicides, industrial chemicals, soils, water, air, biological
tissues and fluids (both human and other animal), and combustion products and
133
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related samples (Taylor et al. 1973; Taylor, Hughes, and Tiernan 1974a,b,c; Fee et
al. 1975; Hughes et al. 1975; Taylor, Tiernan, and Hughes 1974; Tiernan 1975a,b;
Tiernan, Taylor, and Hughes 1975; Taylor et al. 1975, 1976, 1977, 1979; Tiernan et
al. 1979; Erk, Taylor, and Tiernan 1979; Yelton, Taylor, and Tiernan 1977; Wright
State University 1976). The levels of TCDD's in these samples have ranged from
high parts per million (ppm) to low parts per trillion (ppt). A significant number of
samples examined have been found to contain detectable amounts of TCDD's. On
the basis of these findings many investigators believe that TCDD's may already be
widespread contaminants in the environment.
The analytical techniques applied by Brehm Laboratory in these earlier dioxin
programs have varied widely in terms of the complexity of equipment, sample
preparation, and the overall sensitivity and specificity of the procedures. It is now
apparent that a single basic technique, amenable to minor modifications, would be
desirable for the purpose of characterizing various types of chemical samples,
provided that such a technique could satisfy all the specified criteria for sensitivity,
specificity, and other analytical factors.
Sensitivity in the ppt range is required because of the potent toxicity of 2,3,7,8-
TCDD. The current detection capability is approaching 1 ppt in at least some
sample matrices and must be developed in others, particularly chemical process
wastes and sludges. Accuracy is also important in these determinations, owing to
current and potential regulatory actions that hinge on the analytical data.
In 1978 the Brehm Laboratory, in a subcontractual effort with Battelle
Columbus Laboratories, supported through a prime contract between Battelle and
the U.S. EPA, undertook development of new analytical techniques for use in
quantitating ppt levels of TCDD's in various chemical wastes. The goal in this work
was to develop a unified analytical approach to the handling of a variety of
chemical waste sample types and matrices.
The U.S. EPA supplied 17 test samples representing various types of chemical
wastes or residues generated during the manufacture of chlorophenols and related
chemicals. These samples were expected to contain TCDD's and were used in
methods development by the Brehm Laboratory analysts. Presented in this section
are the final results of this work. This section includes a background discussion of
various analytical approaches to the detection of TCDD's, the newly developed
and validated analytical method, a description of the procedures used in
development of the method, and the analytical data obtained in applying the
method to various industrial samples.
BASIC PRINCIPLES OF GAS CHROMATOGRAPHY, MASS
SPECTROMETRY, AND COMBINED SYSTEMS
Gas Chromatography (GC)
Gas chromatography is a special form of chromatography that is used to
separate the components of chemical mixtures. Several excellent references
describe the technique in detail (Dal Nogare and Juvet 1962; Littlewood 1970;
Jones 1970; Ambrose 1971). In gas chromatography the mobile phase is a gas and
the stationary phase is either a liquid or a solid, hence the terms gas-liquid
chromatography and gas-solid chromatography. Gas-liquid chromatography
entails the use of a separation device, which is a column containing the liquid phase
(typically a high-boiling organic silicone polymer) distributed on a highly inert
solid support. Figure 34 depicts a typical gas chromatograph.
The column is maintained in an oven, in which the temperature can be controlled
precisely; through the column is passed an inert, high-purity gas (e.g., helium),
called the carrier gas. The carrier gas is the mobile phase and the organic silicone
polymer is the liquid phase. Typically, the samples are introduced into the column
134
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Fine Adjustment
Valve
Manometer or
I Pressure Gauge
Sample Injector
s\^ Pressure
y^/ Regulator
Cylinder Containing
Carrier Gas
Detector
Column
Thermostat
Figure 34. Apparatus for gas chromatography.
in 0.1 to 10 n\ amounts with a microsyringe through an injection port, which is a
heated (100° to 250° C) inlet system equipped with a silicone septum. The sample is
vaporized immediately upon injection, and the inert carrier gas passing through the
injection port sweeps the volatilized, injected sample out of the injection port and
into the gas chromatographic column. The volatilized constituents of the sample
migrate through the column at varying rates because of variations in the physical
and chemical properties of each component, such as boiling point, absorptivity,
and solubility. The components are thus separated and emerge (elute) from the
column at different times. In some samples the components are highly similar and
are not effectively separated or may necessitate the use of extraordinary
chromatographic procedures. More commonly, however, the components of a
chemical mixture can readily be separated by fairly simple gas chromatographic
techniques.
As each separated component elutes from the gas chromatographic column, it is
detected by one or more of several types of detectors. Among the widely used
detectors are flame ionization, thermal conductivity, and electron capture
detectors. Other, more specific, types of detectors are also used in conjunction with
gas chromatography; in particular, the mass spectrometer has been used
extensively. A discussion of the principles of mass spectrometry follows.
Mass Spectrometry (MS)
Mass spectrometry is described in detail in several references (Beynon 1960;
McLafferty (ed.) 1963; Kiser 1965; Roboz 1968; McFadden 1973). Figure 35 is a
schematic diagram of a typical mass spectrometer; the principal components of
such a system are (1) an inlet system, (2) an ion source, (3) an accelerating system,
(4) an analyzer system, (5) a detector, and (6) a data acquisition system. The
functions of these components are described briefly.
135
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Sample
Reservoir
Inlet
To Vacuum
Oscillograph
Molecular
Leaks
Ion Source
Ionizing Electron Beam
Accelerating Region
Resolving
Slit
Analyzer
Tube
Resonant
Ion Beam
Magnet
Figure 35. Schematic diagram of a Nier 60° sector mass spectrometer
The inlet system is the means of introducing the sample into the ion source of the
mass spectrometer. Inlet devices in common use include heated direct insertion
probes and heated gas inlet systems (batch inlets), which are coupled to the mass
spectrometer through a restricted fixed or variable orifice, often called a "leak." In
recent years the gas chromatograph has been used often to introduce the sample
and is coupled to the mass spectrometer—hence the term "coupled GC-MS."
Because the ion source, the accelerating lens system, the mass analyzer, and the
detector of the mass spectrometer are all maintained under vacuum by a pumping
system, the inlet system must admit the sample (and the carrier gas of a gas
chromatograph) into the spectrometer at such a rate that the pumping system
maintains the specified internal operating pressure of the instrument.
The ion source (shown schematically in Figure 36) is typically maintained at
pressures of 10-3 mm and lower (lO'6 mm) and at temperatures of 100° to
250° C. The source is the region in which ions are generated from the volatile
sample molecules admitted through the inlet system. The ionization of molecules in
the gas phase is effected by bombarding them with electrons emitted from a hot
metal wire or ribbon (the filament) and drawn through a set of slits for collection at
an anode or electron trap. The energy of the electrons is controlled by the potential
difference between the filament and the trap. As these energetic electrons either
strike or pass close to the sample molecules, ionization occurs, producing a
molecular ion that usually is fragmented further to yield other ions of smaller mass.
The ion source produces both positively charged and negatively charged ions, and
many mass spectrometers in use today are designed to detect both types.
The ions produced are electrically forced out of the ion source and into the
accelerating lens system, which generally imparts several kilovolts of energy to the
ions, which then enter the mass analyzer section.
136
-------
CQ
C
5
w
O)
I!
O 3
* 1
o>
® 6'
T D
3 8
M
§ a
-» o'
CO 3
S o,
3
CQ
CD
3
lonization Chamber
,— Repel ler
r— Filament
i— Electron Slit
,— First Accelerating
Slit -— Second Accelerating Slit
Molecular Leak —
Electron Beam —
Anode —
V
Ion Accelerating
Region
-------
The purpose of the mass spectrometer analyzer is to separate the ions according
to their massxharge ratios. Various types of analyzer systems are in use today, and
the type of analyzer usually provides the descriptive name for each mass
spectrometer system. Thus there are, for example, quadrupole mass spectrometers,
single-focusing magnetic deflection mass spectrometers, time-of-flight mass
spectrometers, and double-focusing mass spectrometers. Each of these systems is
characterized by a distinct mode of ion separation, and each provides different
capabilities.
The ability of a mass spectrometer to effect a separation of adjacent mass peaks
(that is, to resolve these peaks) depends upon the analyzer. Resolution is defined by
the equation, R = M/ AM, where M is the mass of the first peak in a doublet and
A M is the difference in the masses of the two peaks. An increase in the value of R
(denoting an increase in resolution) indicates an increase in the ability to
distinguish between very nearly identical masses. Of the several mass spectrometers
mentioned, the double-focusing type affords the greatest mass spectral resolution,
sometimes exceeding 100,000. At this degree of resolution, masses appearing at
m/e 99,999 and m/e 100,000 would be distinguishable. An instrument capable of
such high resolution is of course very complex and expensive and thus would be
used only when such high resolution is mandatory for effective analysis. In
contrast, a quadrupole mass spectrometer is much simpler to operate and less
expensive but can provide only low resolution (m/ Am = 500 to 1000 typically).
Detection of the ions that have been separated is accomplished most often by use
of an electron multiplier, of which, again, various types are in use. An electron
multiplier produces current amplification of 103 to 108 with very low noise level
and with negligible time constant or signal broadening. The amplified analog signal
resulting from the ion impacting on the electron multiplier is finally routed to one
of several possible data acquisition devices; among those often used are the
oscillographic recorder, the analog recorder, a pulse counting device, or the digital
computer.
The data from a mass spectrometer consist, in the analog format, of a spectrum
of peaks (the mass spectrum). The position of each peak on the horizontal axis of a
graphic display indicates its m/ e ratio whereas the amplitude of each peak indicates
the number of ions (or abundance) of that m/e. The data may also be displayed
digitally in tabular form.
If more than one compound enters the mass spectrometer at a given time, then
the masses detected are generally attributable to any or all of the compounds.
Because it is difficult, and sometimes impossible, to interpret the mass spectra
obtained for mixtures of organic compounds, there is great advantage in admitting
the compounds separately. Thus a gas chromatograph is used to introduce the
separated components of a mixture sequentially into the mass spectrometer. The
following is a simplified description of a coupled GC-MS system.
Gas Chromatography/Mass Spectrometry (GC-MS) Systems
In considering the coupling of the gas chromatograph to a mass spectrometer,
one should recall that the source, analyzer, and detector of the spectrometer are all
typically maintained at pressures below 10~5 mm. Therefore, unless the mass
spectrometer is equipped with a very high-capacity pumping system, the gaseous
effluent from a gas chromatographic column cannot be admitted directly to the
mass spectrometer source because this would increase the pressure to a level that
would prevent satisfactory operation. Therefore, coupling is generally achieved by
use of an intermediate device to reduce the rate of flow of the sample and carrier gas
stream. For this purpose several types of devices (called "separators") are used to
achieve partial separation of the carrier gas (typically helium) from the gaseous
sample molecules. Among these devices are (1) a porous barrier or effluent splitter,
(2) a jet/orifice separator, and (3) a molecular separator that includes a permeable
138
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membrane. Some gas chromatograph-mass spectrometer systems feature a direct
coupling of the gas chromatograph with the mass spectrometer by means of a very
high capacity pumping system.
A system that couples a chromatograph with a mass spectrometer is a very
powerful analytical tool, the only system that can provide definitive analysis of
complex chemical mixtures. The separation capabilities of the gas chromatograph
are complimented by the inherent specificity and sensitivity of the mass
spectrometer. During analysis of a complex mixture, the components are separated
gas chromatographically; each eluted component then passes through the interface
(separator) and into the mass spectrometer, which provides and records a mass
spectrum. Typically, the analysis of a mixture could yield several hundred mass
spectra, each containing 100 to 200 mass peaks. Therefore, the computer is an ideal
means of acquiring the mass spectra, reducing the data (converting the acquired
data to actual mass spectra by comparison with calibrated reference files), and
displaying the data. The minicomputer is an essential component of a modern GC-
MS system because the analyses generate-such sizable quantities of data. Use of a
minicomputer can afford other advantages; for example, the computer can be
programmed to control the mass spectrometer so that it monitors only selected
masses typical of the compounds of interest. The computer also can be
programmed to allow monitoring of different masses (corresponding to different
compounds) at different gas chromatographic retention times.
ANALYTICAL BACKGROUND
Analytical methods for detecting TCDD's in various types of samples involve
extensive sample preparation procedures followed by highly complex instrumental
analysis. This section discusses various approaches to the detection and
quantitative measurement of TCDD's, which had been used prior to the inception
of the present study in 1978.
Sample Preparation
Because TCDD's may be found in a variety of matrices, many different sample
extraction/preparation methods have been developed. Although they differ in
complexity, most of these methods may be classified into two major categories:
first, those characterized by a highly basic extraction step, and second, those
involving only neutral extraction. The neutral extraction technique was developed
to preclude the possibility that treatment with a strong base might generate
compounds that could form chlorinated dioxins in the mass spectrometer.
Following extraction, the sample preparation steps are similar for both techniques,
differing only in the method of application and complexity. Both extraction
procedures are described in detail below.
Basic Extraction Method—
Historically, basic extraction methods were first developed for the
determination of TCDD's in environmental samples (Crummet and Stehl 1973;
Baughman and Meselson 1973a; Baughman and Meselson 1973b). Such sample
preparation techniques begin with digestion of a sample aliquot using alcohol and a
strong base. This is followed by a series of organic solvent extractions to separate
the TCDD's from the alkaline mixture. Solvents such as ethanol, hexane,
petroleum ether, and methylene chloride have been used, either singly or in
combination. The solvent extracts are combined and then subjected to a series of
washings with distilled water and strong acid. The washed extract is then treated to
remove all traces of water and passed through one or more chromatographic
columns for removal of some co-extractants, primarily polar compounds.
Instrumental analysis follows.
139
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An example of a typical basic extraction/ preparation technique for nonfat tissue
consists of heating 10 g of sample with 10 ml of ethanol and 20 ml of 40 percent
potassium hydroxide solution for 30 minutes. After the solution cools, an
additional 10 ml of ethanol is added and the solution is extracted with four 10-ml
portions of hexane. The preparation procedure consists of washing the combined
hexane extracts with concentrated sulfuric acid until the acid fraction becomes
only slightly colored. The acid wash is followed by a 10-ml water wash, followed by
evaporation to dryness at room temperature with a stream of dry air. The sample is
then redissolved in hexane and further purified by elution chromatography using
sorbents such as alumina, silica gel, or Florisil, either singly or in combination. The
final eluate is concentrated prior to analysis.
Neutral Extraction Method—
The neutral extraction and preparation technique was originally developed by
O'Keefe, Meselson, and Baughman (1978). Albro and Corbett (1977) describe an
alternative neutral extraction method. A typical neutral extraction technique for
analysis of TCDD's consists of extracting the sample with 10 ml of hexane. The
hexane solution is then chromatographed with a magnesia-Celite 545 column, an
alumina column, an alumina minicolumn, and finally a Florisil minicolumn. The
Florisil column is eluted with methylene chloride, and the eluate is concentrated in
preparation for analysis. It has been asserted that neutral extraction methods are
particularly effective for fish tissues and human milk (O'Keefe, Meselson, and
Baughman 1978; Harless and Dupuy 1979).
Chemical Composition of Extracts—
The sample preparation techniques described above are useful for destroying the
integrity of the sample matrix and yield a small volume of organically
miscible/ soluble residue. The net effect of these clean-up procedures is the
enrichment of the TCDD's relative to the natural components of the sample
matrix, as well as other chlorinated environmental contaminants such as PCB's
and DDE.* The latter compounds are often present in the sample in significantly
greater concentrations than the TCDD's (larger by a factor of 106) and, therefore,
may not be completely removed from the extract at this point. In addition, it is
unlikely that the forgoing procedures result in separation of 2,3,7,8-TCDD from its
other 21 TCDD isomers which may have been present in the sample.**
Consequently, detection and quantitation of TCDD's in general and 2,3,7,8-
TCDD in particular in this "enriched" but still rather chemically complex extract
can only be accomplished by using a highly specific and sensitive instrumental
method. The method of choice, and that described below, is coupled gas
chromatography-mass spectrometry.
Gas Chromatographic and Mass Spectrometric
Methods of Analysis
Because of its ready availability and relative ease of application, gas
chromatography has been extensively used for the detection and quantitation of
TCDD's(Elvidgel971;WilliamsandBlanchfieldl971;Firestoneetal. 1972; Williams
and Blanchfield 1972; Crummett and Stehl 1973; Edmunds, Lee, and Nickels 1973;
WebberandBoxl973;Buser 1976;Bertonietal. 1978).lnmanyinstances,theauthors
*DDE, or 2,2-bis-(p-ch\orophenyl)-l,l-dichloroethylene, is commonly found in environmental samples,
it is a degradation product of the pesticide DDT.
"Subsequent to the completion of the work described herein, reports have appeared in the literature
which describe methods for synthesis and isolation of the 22 TCDD isomers (Nestrick 1979, Dow 1980).
Using such new analytical procedures, it is now possible to isolate and quantitatively determine
2,3,7,8-TCDD in environmental samples even in the presence of the other 21 isomers.
140
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cited above have found that the chromatographic methods lack the required
specificity for determining TCDD's in complex samples. Consequently these
researchers and others have sought more sensitive and specific methods of detection.
At present the analytical method which is almost exclusively used for the detection
and quantitation of TCDD's is coupled gas chromatography-mass spectrometry or
GC-MS(Crummettand Stehl 1973;Tiernanetal. 1975;Tayloretal. 1975;Buserand
Bosshardt 1976; Harless 1976; Buser 1977; Gross 1978).
GC-MS is the only known method that can provide very high sensitivity as well
as the required selectivity for TCDD's. A particularly sensitive and specific GC-
MS technique which has been used entails low-resolution selective ion monitoring.
In the case of TCDD's, fragment ions at nominal m/e 320 and m/e 322, as shown
below, are monitored.
-V S~
©
70 eV
Cl
= m/e 319 8966 (nominal m/e = 320)
35..-I ©
electrons
1a>N^oA^%.
C12H437CI35CI302+
•/ ^ = m/e 321.8936 (nominal m/e = 322)
The intensities of these ions are recorded as the TCDD's elute from the gas
chromatograph. The ratio of the intensities of m/e 320 to m/e 322 is a characteristic
indicator of TCDD's. Unfortunately, other compounds which may also be present in
the sample extract can also give rise to mass spectral ionsat the same nominal masses
(m/ e 320and m/ e 322) as TCDD's. Two approaches can minimize this problem.
The first approach utilizes high resolution mass spectrometry (M/ AM > 9000) to
increase the selectivity. The ions appearing under low-resolution MS conditions at
nominal mass 322 may be produced from TCDD's which have C^^C^O^ as
their elemental composition and thus have an "exact" mass of 321.8936. Interfering
ions such as pentachlorinated biphenyls may also appear at nominal mass 322, but
their elemental composition is C|2H3C15, and therefore they have an "exact" mass
of 321.8677. Thus, using high-resolution MS these ions of slightly different mass
are distinguishable, and so the dioxin component having the exact mass of
321.8936 can be reliably measured. Conceivably, ions having the C^^C^O^
composition can be produced from other compounds, but proper selection of
chromatographic procedures maximizes the possibility of separating such
compounds from TCDD's. The achievement of detection limits in the low-ppt
range at high MS resolution generally requires the use of data acquisition methods
which entail signal averaging (Shadoff and Hummel 1978; Gross 1978; Taylor etal.
1976).
A second approach to the problem of separating TCDD's from closely related
interferences makes use of low-resolution massspectrometrybutincorporatesamore
selective separation step prior to the mass spectrometric analysis. Capillary column
gas chromatography is useful for this purpose (Buser 1977), but liquid
chromatography followed by capillary column gas chromatography hasprovedeven
morefruitful(Nestrick, Lamparski,and Stehl 1979; Dow 1980).
In both the GC-high-resolution and the GC-low- resolution mass spectrometric
methods, internal standards are frequently used for the quantification of TCDD's.
The analytical method developed in the present study utilizes an internal standard,
namely 37d4-2,3,7,8-TCDD.
141
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ANALYTICAL METHOD*
The analytical procedure ultimately developed and described herein for
determination of TCDD's in various industrial process waste samples utilizes two
separate GC-MS systems. A gas chromatograph coupled to a low-resolution
quadrupole mass spectrometer (GC-QMS) is used for preliminary identification of
TCDD's in the extracts of the waste samples. A second apparatus coupling a gas
chromatograph and a high-resolution mass spectrometer (GC-MS-30) is used to
confirm the results obtained with the GC-QMS technique. The analysis method
entails two steps, sample preparation and instrumental analysis, as described
below. It should be emphasized that, even with the elaborate separation techniques
employed here, the 2,3,7,8-TCDD isomer is still not resolved from the other TCDD
isomers if these are present in the sample extracts. As a result, the quantitative data
obtained here for TCDD's must be considered an upper limit rather than an
absolute level for any individual TCDD isomer.
Sample Preparation
The following procedures were developed as an approach to preparation of
industrial waste samples and have been successfully applied in this study.
1. Place a 2.0 g aliquot of the sample in each of the two extraction vessels. To
each aliquot, add an appropriate quantity of 37Cl4-2,3,7,8-TCDD
dissolved in "distilled-in-glass" benzene as an internal standard. Spike one
of the two aliquots with an additional known quantity of authentic native
2,3,7,8-TCDD at a concentration equal to the nominal amount expected in
the sample.
2. Add 30 ml "distilled-in-glass" petroleum ether to each sample and mix
thoroughly.
3. Extract each organic solution with 50 ml of double-distilled water and
discard the aqueous layer.
4. Extract each solution with 50 ml of 20 percent potassium hydroxide and
discard the aqueous basic layer.
5. Extract each solution with 50 ml of double-distilled water and discard the
aqueous portion.
6. Extract each solution with 50 ml of concentrated sulfuric acid and discard
the aqueous acidic layer.
7. Repeat step 6 until the acid layer is nearly colorless.
8. Extract each organic solution with 50 ml of double-distilled water and
discard the aqueous layer.
9. Dry each organic solution over anhydrous sodium sulfate.
10. Quantitatively transfer each organic solution to another vessel, and
concentrate to a volume of approximately 1 ml by passing a stream of
purified nitrogen over the surface of the liquid while applying gentle heat
(50° C) to the vessel.
11. Construct a chromatography column for each sample by packing a
disposable glass pipette (I.D. = 0.8 cm) with glass wool and 2.8gof Woelm
basic alumina (previously activated by maintaining it at 600° C for a
minimum of 24 hours, then cooled in a dessicator for 0.5 hour prior to use).
12. Quantitatively transfer each concentrated organic solution to the top of a
column.
13. Elute each column with 10 ml of 3 percent "distilled-in-glass" methylene
chloride in "distilled-in-glass" hexane, and discard the entire column
effluent.
'This section presents the analytical method only; discussion of development of the method follows in the
next subsection.
142
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14. Elute each column with 20 ml of 20 percent methylene chloride in hexane
and collect the eluate in four 5-ml fractions.
15. Elute each column with 10 ml of 50 percent methylene chloride in hexane
and retain the entire column eluate for analysis.
16. Elute each column with 3 ml of 50 percent methylene chloride in hexane
and retain the eluate for analysis.
17. Concentrate all six fractions in benzene to an appropriate volume (usually
0.1 to 1.0 ml) and proceed with analysis.
Instrumental Analysis
The application of GC-MS instrumentation methods for analysis of TCDD's
requires knowledgeable and experienced personnel, dedication of the equipment,
and significant capital and operating costs. The requirement for detecting low ppt
levels of TCDD's in these analyses necessitates such a sensitive and selective
analytical method. Because this is currently the only known method which meets
these criteria, the relatively high expense is unavoidable.
The following is a brief description of the instrumentation required for the
analytical prodedures developed herein.
GC-QMS System—
The GC-QMS system consists of a Varian Model 2740 Gas Chromatograph
coupled directly (no helium separator is required) to an Extra-nuclear Quadrupole
Mass Spectrometer. The GC was adapted to include a sophisticated system of
remotely actuated high-temperature switching valves (Valco Co.) and Granville-
Phillips molecular leak valves, so that the column effluent could be readily
regulated (Tiernan et al. 1975a; Erk, Taylor, and Tiernan 1978).
With this arrangement, the total column effluent can be directed into the mass
spectrometer ion source, or the effluent flow can be split, one portion going to the
ion source and the other to a gas chromatographic detector, as desired. The use of a
differential high-speed pumping system on the source vacuum envelope permits
introduction of as much as 65 ml/min of effluent from the gas chromatograph into
the mass spectrometer ion source. Admitting the total chromatograph effluent into
the mass spectrometer source enhances the sensitivity of the analysis.
For purposes of instrument control and data acquisition, the GC-QMS system is
coupled to an Autolab System IV Computing Integrator. Additional capacity for
off-line data reduction is available with a Hewlett-Packard 2116C Minicomputer,
which is programmed to accept data (punched paper tape) from the system when
necessary.
GC-MS-30 System—
The GC-MS-30 system used in these studies consists of a Varian 3740 Gas
Chromatograph coupled through an AEI silicone membrane separator to an AEI
MS-30 Double-Focusing, Double-Beam Mass Spectrometer. The mass
spectrometer is equipped with a unique electrostatic analyzer scan circuit
developed by Wright State University, which permits the monitoring of as many as
four mass peaks, essentially simultaneously, by rapidly and sequentially stepping
and switching between the masses of interest, while maintaining picogram
sensitivity for TCDD's. The data are recorded by use of a Nicolet 1074 Signal
Averaging Computer.
Sample Analysis—
Analysis consists of three steps as described below.
1. Analyze each eluate fraction (collected in the elution chromatography
separation of the sample) on the low-resolution GC-QMS, using the
following operating parameters:
143
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Varian 2740 Gas Chromatograph
Column: 2 m x 3 mm I.D. glass packed with
3 percent OV-7 on Gas Chrom Q
Carrier gas: Helium at 65 ml/min (the total chromatographic
column effluent is admitted to the mass
spectrometer ion source)
Temperatures: Injector: 255° C
Column: 275° C
Transfer line: 295° C
Quadrupole Mass Spectrometer
Ionizing voltage: 23.5 eV
Multiplier: 3200 V
Resolution: 1:350
Source envelope
pressure: 1.4 x 10-4 torr
Analyzer envelope
pressure: 8.0 * 10'6 torr
Masses monitored: m/e 320, 322
Source temperature: 250° C
Analyzer temperature: 120° C
2. Confirm any samples showing positive levels of TCDD's on the low-
resolution GC-QMS by analysis of the corresponding eluate fractions
using high-resolution GC-MS-30 and the following operating parameters:
Varian 3740 Gas Chromatograph
Column: 1.8 m x 2 mm I.D. coiled glass column
packed with 3 percent Dexsil 300 on
Supelcoport (100/120 mesh)
Carrier gas: Helium at a flow rate of 30 ml/min
Temperatures: Injector: 250° C
Column: 240° C
Transfer line: 285° C
AEI MS-30 Mass Spectrometer
Resolution: 1:12,500
Ionizing voltage: 70 eV
Masses monitored: m/e 319.8966, 321.8936, 325.8805, and
327.8846
Temperatures: Membrane separator: 215° C
Transfer line: 270° C
Source: 250° C
3. Determine the overall recovery of the analytical prodedure by measuring
the amount of internal standard (37Cl4-2,3,7,8-TCDD) recovered.
DISCUSSION AND RESULTS
For use in developing and demonstrating the analytical methodology for
determination of ppt levels of TCDD's in process wastes and related materials,
samples were provided that were representative of wastes from several different
industrial chemical processes that might be expected to generate chlorodioxins.
The samples were obtained by the U.S. EPA from plants manufacturing
trichlorophenol, pentachlorophenol, and hexachlorophene, and from plants
processing wood preservatives. Initially, the nature and identity of each sample
144
-------
were unknown to the Wright State investigators, although information was made
available early in the program about two of the samples originating from
trichlorophenol manufacturing processes. Subsequently, identifying data on most
of the remaining samples were obtained and are summarized in Table 22.
TABLE 22. SAMPLES USED IN DEVELOPMENT OF ANALYTICAL
METHOD FOR TCDD'S IN INDUSTRIAL WASTES
EPA No.
C04130
C04131
C04132
2
3
4
5
6
12700
12701
12702
11020
11021
11022
11023
11024
11025
Sample type
Liquid slurry
Solid
Liquid
Liquid/solid
Slurry
Slurry
Liquid/solid
Liquid
Liquid/solid
Liquid
Solid
Liquid/solid
Liquid
Liquid/solid
Solid
Solid
Solid
Source and identity of sample
Givaudan: aqueous slurry of
hexachlorophene
Givaudan: activated clay filter cake from
hexachlorophene manufacturing
Givaudan1 ethylene dichloride recovery solution
from hexachlorophene manufacturing
Transvaal' still bottom from trichlorophenol (TCP)
manufacturing
Transvaal: cooling tank bottom from TCP
manufacturing
Transvaal: discharge line from TCP
manufacturing
Transvaal: sludge from TCP manufacturing
Transvaal: type unknown; presumably TCP
process sample
Reichold Chemical: sludge from intake of
settling pond, pentachlorophenol
(PCP) manufacturing
Reichold Chemical, sludge from discharge of
settling pond, PCP manufacturing
Reichold Chemical PCP manufacturing
Baxter, retort solids residue from wood
preserving
Baxter1 storage tank solution from wood
preserving
Baxter: cooling water solids from wood
preserving
Baxter, treated wood from wood preserving
Baxter: soil from neighborhood of wood
preserving plant
Baxter: sludge from wood preserving
145
-------
Because still bottom samples collected at a trichlorophenol manufacturing plant
were considered of major interest, a sample of this type (EPA sample 2) was
selected for use in preliminary investigations.
The initial approach to analytical method development, based on the experience
of Wright State personnel in chlorodioxin analysis, is outlined below.
1. If the sample is solid, dissolve a portion in an immiscible combination of
aqueous and organic solvents, such as water and petroleum ether. If the
sample is a liquid, extract a portion of the material with a similar water-
organic solvent system. In the absence of any prior knowledge about the
content of TCDD's in a given sample, the quantity to be extracted must be
selected on the basis of sensitivity of the overall technique (as indicated by
previous experience) and the desired limits of detection.
2. Separate the aqueous component of the sample-solvent mixture from the
organic phase, and discard the aqueous portion.
3. Extract the organic fraction with sequential washes of acid, water, base,
water, acid, and water (in that order), and discard the washes.
4. Concentrate the remaining organic phase to near dryness and elute through
an alumina column, using appropriate solvents to separate the TCDD's
and other sample components.
5. Concentrate the fraction containing TCDD's and subject it to preliminary
screening analysis by use of the GC-QMS system, operated in the selected-
ion monitoring mode and adjusted to detect m/e 322 and m/e 320, the two
most abundant peaks in the isotopic molecular ion cluster of 2,3,7,8-
TCDD.
6. If the initial screening indicates a positive level of TCDD's, then the level
must be confirmed and quantitated by use of the GC-MS-30 system.
This approach was used in analysis of sample 2. Subsequent modifications of this
initial procedure and other observations are discussed in following subsections.
Developing Sample Preparation Technique
Four aliquots of sample 2 were extracted with a mixture of water and petroleum
ether. The aqueous portion was discarded, and each organic fraction was washed
successively with acid, water, base, water, acid, and water. The samples were then
concentrated and transferred to a 2.8 g Woelm basic alumina column (length 12
cm, I.D. 0.8 cm).
Large quantities of a white crystalline substance appeared in the column eluate.
The column apparently was overloaded owing to the large quantity of this material
present in the sample. This substance possibly accounted for interference in the
mass chromatogram (Figure 37). Adjustments of the column chromatography
procedure were therefore made in an effort to eliminate this crystalline
contaminant in the fraction containing the TCDD's.
A solvent screening study was done to evaluate the solubility of the contaminant
and the potential for its removal from the sample matrix. Results are as follows:
Solvent tested Solubility of contaminant
100% methanol Slight solubility
3% methylene chloride Solubility slightly greater than
in hexane in 100% methanol
25% carbon tetrachloride Solubility slightly greater than
in hexane in 3% methylene chloride
in hexane
100% methylene chloride Completely soluble
146
-------
TCDD's
Time
Figure 37. Mass chromatogram of extract of sample 2, at m/e 322
obtained with GC-QMS.
Next, elution characteristics of the alumina column were evaluated. Table 23
presents the solvents and the discrete fractions collected in determining the elution
characteristics of the Woelm basic alumina column.
Selection of the solvents and the eluate fractions was based on earlier experience
of Brehm Laboratory personnel in column chromatography with similar sample
matrices.
The eluate fractions were analyzed for TCDD's by use of the GC-QMS system.
The results, presented in Table 24, show clearly that the best elution sequence
involves the use of 10 ml of 3 percent methylene chloride in hexane, followed by 18
ml of 20 percent methylene chloride in hexane. This sequence yields TCDD's in a
well-defined fraction containing few other contaminants. Use of all the other
solvent pairs yielded fractions that generated interferences in the dioxin mass
chromatogram which were as great as those shown in Figure 37 or greater.
147
-------
TABLE 23. ELUTION OF TCDD'S IN EXTRACTS OF SAMPLE 2
Set no.
A1
Eluting solvent
3% methylene chloride
Total volume
of column
effluent (ml)
10
Volume of fraction (s)
collected
total 10 ml
in hexane
A2 50% methylene chloride
in hexane
B1 3% methylene chloride
in hexane
B2 20% methylene chloride
in hexane
C1 25% carbon tetrachlonde
in hexane
C2 50% methylene chloride
in hexane
D1 25% carbon tetrachlonde
in hexane
D2 20% methylene chloride
in hexane
13 1 st 5 ml in one fraction; 6th
through 13th ml in separate
1-ml fractions
10 total 10 ml
18 1st 5 ml in one fraction; 6th
through 13th ml m separate
1-ml fractions; 14th through
18th ml in one fraction
10 total 10 ml
13 1st 5 ml in one fraction; 6th
through 13th ml in separate
1-ml fractions
10 total 10 ml
18 1st 5 ml m one fraction; 6th
through 13th ml in separate
1-ml fractions, 14th through
18th ml in one fraction
Application of Initial Procedure to EPA Samples—
The extraction and sample preparation procedure developed for sample 2 was
applied to ten of the other industrial samples supplied by EPA. In these analyses
some interferences were still present in the extract fraction which was thought to
contain the TCDD's; the interferences resulted in a higher minimum detection limit
(ppb) than was desired. Portions of these samples were also spiked with known
quantities of 2,3,7,8-TCDD so that recoveries for the procedure could be
determined. The recovery in GC-QMS analysis of sample 2 was 127 percent.
Surprisingly, in analysis of the other ten samples by the same procedure, none of
the added 2,3,7,8-TCDD was recovered. The same procedure was then applied in
analyses of spiked aliquots of these samples, but this time all the eluate fractions
from the alumina columns were retained and analyzed for TCDD's. Again, no
2,3,7,8-TCDD was detected. It was necessary to further investigate the sample
preparation procedures.
Optimizing Sample Preparation Procedure—
Another sample (CO4131) was subjected to the general preparation procedure
already described, up to the point of elution of the column. Then the sample was
148
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TABLE 24. CONTENT OF TCDD'S IN COLUMN FRACTION FOR SAMPLE 2a
Solvent
set no. 1 2
A1 -* -*
B1 - -
C1 oo
D1 oo
Eluate fraction no.b
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
TCOD's detected
-*-*-*-*-*-*-*-* o o o o o o o o
--------oooooooo
oooooooo
oooooooo
a—Aliquots of EPA sample 2
b—Fraction numbers refer to those collected from each of the columns, as indicated in Table 23.
+ = TCDD's present in fraction
- = No TCDD's detected infraction
o = Fraction not analyzed
* = Two or more peaks evident in mass chromatogram near 2,3,7,8-TCDD retention time.
-------
spiked with a large quantity of 2,3,7,8-TCDD by introducing it directly onto the
alumina column. The column elution characteristics were then evaluated as before
and the results are shown in Table 25. This procedure was repeated for all other
samples and their column elution profiles were determined.
TABLE 25. RECOVERY OF 2,3,7,8-TCDD SPIKE FROM ELUATES
OF SAMPLE CO4131
No. of fractions Volume of
Solvent collected each fraction Action
Results
10 ml 3%
methylene
chloride
in hexane
20 ml 20%
methylene
chloride
in hexane
10 ml 50%
methylene
chloride
in hexane
10 ml Discarded
5 ml Analyzed by No 2,3,7,8-TCDD
GC-QMS
10ml Analyzed by 80% 2,3,7,8-TCDD
GC-QMS recovered
This study indicated that a general extraction and preparation procedure must
include a provision for assessing the elution characteristics of the alumina column
for each type of sample matrix. Apparently, each type of sample conditions or
deactivates the column in a manner peculiar to its matrix, and this conditioning, in
turn, determines the elution characteristics of TCDD's, which may differ markedly
in different sample types.
Analytical Procedure
Research workers in several laboratories, including the Brehm Laboratory, have
analyzed various types of samples for dioxin content. Generally, the analytical
approach to determining a chlorinated hydrocarbon of this type in a complex
sample matrix has involved quantitation of the chlorocarbon by use of electron
capture-gas chromatography (EC -GC) or gas chromatography-mass spectrometry
(GC-MS). The studies at Brehm Laboratory entailed use of GC-MS and high -
performance liquid chromatography (HPLC).
GC-MS System—
As described in the subsection entitled "Analytical Method," the GC-QMS
system was used for initial detection of TCDD's in the fractionated sample. Then
GC-MS-30 was used to confirm the positive levels of TCDD's detected in the GC-
QMS.
In one procedural modification, a labelled internal standard, 37Cl4-2,3,7,8-
TCDD, was added to all samples. Also, the MS-30 high-resolution mass
spectrometer was modified to permit essentially simultaneous step-scanning of
four ions in the high-resolution mode. The ions typically monitored were:
150
-------
m/e 319.8966, a major molecular ion in the mass spectrum of
2,3,7,8-TCDD
m/e 321.8936, a major molecular ion in the mass spectrum of
2,3,7,8-TCDD
m/e 325.8805, a molecular ion indicative of interfering PCB's
m/e 327.8846, a major molecular ion in the mass spectrum of
37C14-2,3,7,8TCDD.
High-Performance Liquid Chromatography (HPLC)—
In earlier studies aimed at determining TCDD's in environmental samples,
concern has been raised that the presence of these -called predioxins (for example,
polychlorinated phenoxyphenols) in the samples would lead to false positive
determinations of TCDD's because the latter can be formed by cyclization
reactions of the predioxins in the hot injection port of gas chromatographs. The
present investigation ruled out potential false positive effects of predioxins by
applying an HPLC analytical technique as a quality assurance measure. HPLC
does not entail injection of the sample into a heated port and therefore minimizes
the possibility of thermal cyclization of predioxins.
The HPLC instrument used in these studies is the Model LC 5021 Varian. This
microprocessor-controlled HPLC is both completely automatic and
programmable and incorporates a multiple solvent system. Three detectors are
available: a fixed-wavelength UV (254 nm) detector, a variable-wavelength UV
detector, and a flourescence detector. A cathode ray tube (CRT) keyboard unit
displays operating parameters while a micropressor-based computing integrator
(DCS-111L) stores the data and performs appropriate calculations. The
parameters applicable to the instrument as it was used in this study are listed below:
Column: DuPont Zorbax ODS
(25 cm x 6.2 mm)
Temperature: 50° C
Starting pressure: 952 psig
Solvent: 100% methanol
Flow rate: 2.5 ml/min
Detector: UV (235 nm)
Sensitivity: 0.02 absorbance units full
scale/15 mg TCDD's
Upon injection of a 10 /J.I aliquot of the sample 2 extract into the HPLC, a
chromatographic peak having a retention time which was the same as that observed
with the 2,3,7,8-TCDD standard was observed. Representative HPLC
chromatograms are shown graphically in Figures 38 and 39, and these results
indicate a readily detectable level of TCDD's in the sample 2 extract. It is apparent
that the TCDD's detected cannot have been formed by cyclization of predioxins.
Analytical Results—
Attempts were made to extract 15 of the 17 EPA samples by the procedures
described in the subsection on the analytical method. The remaining two samples,
11023 and 12702, were not subjected to these methods. Sample 11023 was a section
of wood, which the earlier experience of Wright State had shown is not amenable to
a potassium hydroxide digestion process. Sample 12702 was not analyzed because
of insufficient time during the contract period.
151
-------
TCDD's
Time
Figure 38. High pressure liquid chromatogram of sample 2.
152
-------
2,3,7,8-TCDD
Time
Figure 39. High pressure liquid chromatogram of 2,3,7,8-TCDD standard.
153
-------
Twelve of the 15 samples were successfully analyzed by the Wright State
procedure, with results as shown in Table 26. These data show that the procedure is
applicable to samples exhibiting a wide range of concentrations of TCDD's from
ppt to ppm (a factor of 10"). For those samples in which no TCDD's were
detected, the minimum detectable concentration oi TCDD's was in the low ppt
range (45 to 140 ppt).
TABLE 26. RESULTS OF GC-MS-30 ANALYSIS OF EPA SAMPLES
FOR TCDD'S
EPA sample no.
C04130
C04131
CO4132
2
3
3
5
6
12700
12701
12702
11020
11025
11021
11022
11023
11024
Origin
Givaudan
Givaudan
Givaudan
Transvaal
Transvaal
Transvaal
Transvaal
Transvaal
Reichold
Reichold
Reichold
Baxter
Baxter
Baxter
Baxter
Baxter
Baxter
Quantity of
TCDD's found
ng/g (ppb)
NDa
ND
ND
40,000
675
22
70
ND
ND
ND
b
ND
ND
c
c
b
d
Minimum detectable
concentration
pg/g (ppt)
140
70
50
e
e
e
e
50
80
75
140
45
a—ND' No TCDD's detected in excess of the minimum detectable concentration
b—Not processed
c—General procedure could not be successfully applied to these samples
d—Not analyzed on GC-MS-30
e—An exact minimum detectable concentration was not recorded for these analyses, however, the
reported values for quantity of TCDD's found are well above the criterion of 2 5x noise
Examples of mass fragmentograms obtained with the GC-MS-30 high
resolution mass spectrometer are shown in the following figures. Figure 40 shows a
four-ion step-scan mass f ragmentogram of benzene, the solvent used for dilution of
the final sample residue. Analysis of a solvent blank is repeated before analysis of
each sample in order to ensure that no TCDD's are carried over in the injection
syringe. Figure 41 illustrates similar data obtained from injection of a sample
consisting of 50 pg of native 2,3,7,8-TCDD and 1 ng of 37Cl4-2,3,7,8-TCDD.
Note that different attenuations have been applied to the various peaks displayed in
Figure 41. Figures 42 and 43 demonstrate similar four-ion step-scan mass
fragmentograms obtained for two of the EPA samples. Although the
fragmentogram for sample 12700 shows peaks at m/e 319.8966 and m/e 321.8936,
their intensities are not greater than 2.5 times the background; this is one of the
154
-------
m/e 327 8846
Attenuation. 512
m/e 319.8966
Figure 40. Four-ion mass fragmentogram of benzene solvent blank
obtained with GC-MS-30
Attenuation- 256
m/e 321.8936
m/e 319.8966
m/e 327.8846
Attenuation. 8192
m/e 325 8805
m/e 321 8936
Figure 41. Four-ion mass fragmentogram of 50 pg 2,3,7,8-TCDD and
1 ng 37CI4-2,3,7,8-TCDD obtained with GC-MS-30.
155
-------
00
CO
CM
CO
0
\
E
CM
CO
co
CO
o
00
CN
m
-------
CD
00
s
CM
CO
0)
IN
5
Figure 43. Four-ion mass fragmentogram of sample 5
obtained with GC-MS-30.
157
-------
criteria applied for establishing the presence of TCDD's in a sample. Based on the
recovery of "Cl4-2,3,7,8-TCDD from sample 12700, the minimum detectable
concentration (MDC) of TCDD's is 80 pg/g.
The mass fragmentogram for sample 5 (Figure 43) shows peaks at both m/e
319.8966 and m/e 321.8936, and the intensities are well in excess of 2.5 times the
background levels. After application of a recovery correction on the basis of the
internal standard, these data indicate that sample 5 contains 70 pg TCDD's per
gram of sample. Data similar to those shown in Figures 40 through 43 were
obtained for the other samples analyzed in this program.
Analyses of samples 11021 and 11022 were not completed owing to the
formation of an intractable emulsion at the petroleum/ether interface. Analysis of
sample 11024 on the GC-MS-30 system was not attempted because a colored
residue was visible in the final extract. Earlier experience had shown that such
residues indicate that the sample extract contains gross quantities of compounds
other than TCDD's, which lead to serious contamination of the high-resolution
mass spectrometer.
All data in Table 26 were derived from analyses with the high resolution GC-
MS-30 system. For each of the industrial process samples, the appropriate elution
chromatogram fractions to be analyzed were determined in advance in a series of
alumina column elutions using an aliquot of the sample spiked with 2,3,7,8-TCDD
standard; these elutions were accomplished in a manner similar to that described
for sample 2. These elution test samples were analyzed with the low resolution
GC-QMS system. Data pertinent to the determination of the elution characteristics
of TCDD's in the various samples are shown in Table 27. The fractions collected
for each sample in the elution experiments are as follows:
1. Fraction I—First 5-ml portion eluted with 20 percent methylene chloride in
hexane.
2. Fraction II—Second 5-ml portion eluted with 20 percent methylene
chloride in hexane.
3. Fraction III—Third 5-ml portion eluted with 20 percent methylene
chloride in hexane.
4. Fraction IV—Fourth 5-ml portion eluted with 20 percent methylene
chloride in hexane.
5. Fraction V—First 10-ml portion eluted with 50 percent methylene chloride
in hexane.
6. Fraction VI—Last 3-ml portion eluted with 50 percent methylene chloride
in hexane.
These fractions were analyzed with the GC-QMS in reverse order, beginning
with the last fraction and continuing backward until the quantity of TCDD's
detected in the several fractions was a reasonably large percentage of that originally
added as the spike, or until a fraction was reached that contained no TCDD's. The
data in Table 27 show that TCDD's are completely eluted from all samples prior to
Fraction VI. In most cases the bulk of the TCDD's appeared in Fraction V,
although in samples 11020 and 11024 the TCDD's were detected in Fraction IV.
Table 28 summarizes the total recoveries of the added 2,3,7,8-TCDD spikes
achieved by collecting the optimum column chromatography fractions of the
various industrial process samples. These recoveries range from 60 to 102 percent,
with a mean value of 85 percent.
Except for sample 2, all of the samples processed in this investigation were also
spiked with 37Cl4-2,3,7,8-TCDD. This compound was added as an internal
standard in the analyses with the GC-MS-30 system. The mean recovery of 37C14-
2,3,7,8-TCDD for the samples analyzed herein was 74 percent with a standard
deviation of 16.8 percent. The recovery data are shown in Table 29.
158
-------
Confirmation of TCDD's in Sample 2—
Measurements in which m/e 320 and m/e 322 were monitored by the low-
resolution GC-QMS system indicated that sample 2 contained approximately 40
^ig TCDD's per gram of sample. The report of this high level of TCDD's prompted
considerable concern both at EPA and state regulatory organizations.
This finding was also controversial because an earlier examination of this sample
in an EPA laboratory had yielded no indication of the presence of TCDD's. It was
obviously important, therefore, to more definitively confirm the initial Wright
State analyses of sample 2; this was done by a procedure essentially the same as that
which is described as the final method.
TABLE 27. TCDD ISOMER CONTENT OF COLUMN FRACTION SAMPLES
SPIKED WITH 2,3,7,8-TCDD
Quantity of Quantity of
EPA
samples3
CO4130
3
12700
12701
11020
1 1 024d
11025
Eluate
fractionb
IV
V
VI
V
III
IV
V
VI
IV
V
VI
IV
V
IV
V
VI
IV
V
VI
IV
V
2,3.7,8-TCDD
added to
sample
(ng/g)
1042
1035
5064
12.14
12.84
986
371
6.54
2.3,7,8-TCDD
detected in
fraction0
(ng/g)
ND
1062
ND
597
ND
46
625
ND
ND
8.4
ND
ND
10 12
056
868
ND
0.29
1.09
ND
ND
5.63
Minimum
detectable
concentration
(ng/g)
050
0.50
3.00
300
0.30
0.57
0.28
0.23
0.08
0.14
Recovery
(%)
102
69
79
6
88
8
29
86
a—See Table 22 for description of sample
b—Designation of eluate fractions.
Ill Third 5-ml aliquot eluted with 20% methylene chloride in hexane
IV Fourth 5-ml aliquot eluted with 20% methylene chloride in hexane
V First 10-ml aliquot eluted with 50% methylene chloride in hexane
VI Last 3-ml aliquot eluted with 50% methylene chloride in hexane
c—ND. no 2,3,7,8-TCDD detected in excess of the minimum detectable concentration.
d—Portion of sample was lost during preparation
159
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TABLE 28. RECOVERIES OF 2,3,7,8-TCDD-SPIKED SAMPLES
FOLLOWING ALUMINA COLUMN CHROMATOGRAPHY
EPA
samples
CO4130
4
5
6
12700
12701
11020
11024
11025
Quantity of
2,3,7,8-TCDD
added (ng/g)
(ppb)
10.4
120
12.2
10.4
12.1
128
9.9
37
6.5
Quantity of
2,3,7,8-TCDD
detected (ng/g)
(ppb)
10.60
840
11.00
9.70
8.40
1010
9.24
1 38
560
Recovery
(%)
102
70
90
93
69
79
94
37a
86
a—Portion of sample lost during preparation
TABLE 29. RESULTS OF GC-MS-30 ANALYSES OF SAMPLES
SPIKED WITH 37CI4-2,3,7,8-TCDD
EPA
samples
C04130
CO4131
CO4132
5
6
4
12700
12701
11020
11025
wsu
samples
B-001C
B-002A
B-003A
B-006A
B-007A
B-008A
B-009E
B-010E
B-012F
B-017B
Quantity of
37CI-2,3,7,8-TCDD
added (ng/g)
(ppb)
1 11
0.93
0.96
1 21
1.09
1 09
1 23
1 29
1 19
0.67
Quantity of
37CI-2,3,7,8-TCDD
detected (ng/g)
(ppb)
0.78
091
0.61
048
0.67
0.75
1 06
1 14
0.93
058
Recovery
(%)
70
98
64
40
61
69
86
88
78
86
a—Data for samples 2 and 3 are not included because the ratio technique could not be used with
samples containmg high levels of TCDD Sample 11024 is also omitted because the extract was
not clean enough for analysis by GC-MS-30
160
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The sample was extracted, and the extract was subjected to liquid
chromatography preparation. As mentioned earlier, the fraction of sample 2 that
was eluted from the alumina column with 20 percent methylene chloride in hexane
was determined to contain the bulk of the TCDD's. Accordingly, this fraction was
analyzed for TCDD's by the GC-MS-30 system operated in the dual-ion
monitoring mode (m/e 319.8966 and 321.8936 were monitored). The resolution of
the MS-30 mass spectrometer was adjusted to 1:12,500 for this measurement.
The dual-ion step-scan mass fragmentogram obtained with this sample extract is
shown in Figure 44 and corresponding data obtained with an authentic 2,3,7,8-
TCDD standard are shown in Figure 45. For EPA sample 2, the ratio of m/e
319.8966 to m/e 321.8936 in the mass fragmentogram is 0.79, while that for the
2,3,7,8-TCDD standard is 0.84. Both of these values agree well with the
theoretically predicted ratio of these two peaks, 0.77, which is calculated on the
basis of the relative abundance of 35C1 and 37C1 isotopes.
m/e 321.8936
m/e 319.8966
Figure 44. Dual-ion mass fragmentogram of sample 2 obtained with
GC-MS-30, mass resolution 1 12,500.
161
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m/e 321.8936
m/e 319.8966
Figure 45. Dual-ion mass fragmentogram of 150 pg of 2,3,7,8-TCDD standard
obtained with GC-MS-30, mass resolution 1:12,500
Further confirmation that the unknown component in sample 2 is indeed a
quantity of TCDD isomers is provided by the observation that the GC retention
time of the unknown component was identical to that of the 2,3,7,8-TCDD
standard. This criterion is applied in all determinations of TCDD's in Wright
State's Brehm Laboratory.
The mass spectrometric resolution achieved in this program with the MS-30
Mass Spectrometer can be demonstrated experimentally by using the specialized
step-scan circuitry developed by Wright State. The practical method of
demonstrating the resolution is to obtain a narrow mass scan for a sample
consisting of TCDD's in a mixture of other compounds that yield mass spectral
ions whose mass is very close to that of TCDD's. In earlier studies we utilized a
mixture of 2,3,7,8-TCDD, PCB's such as Aroclor 1254, and DDE* for this
purpose. The latter compounds yield mass spectral peaks that are very near the
mass of the TCDD's major ion (Aroclor 1254 m/e 321.8679, DDE m/e 321.9290,
2,3,7,8-TCDD m/e 321.8936).
In order to obtain ions of approximately equal intensity from all these
compounds, however, the quantities of PCB and DDE must be quite large relative
to the quantitiy of TCDD's. Figure 46 shows a typical mass fragmentogram
obtained during this investigation in analyses of two mixtures of 2,3,7,8-TCDD
and DDE and a mixture of Aroclor 1254, 2,3,7,8-TCDD, and DDE. On the basis of
the data shown in Figure 46, the dynamic resolution of the mass spectrometer is
calculated to be 14,000 with 20 percent valley definition.
The data on sample 2 which were described above were based on monitoring
only m/e 320 and m/e 322 in the mass spectrum of TCDD's. Our earlier experience
had shown that the low levels of TCDD's that are usually found in environmental
samples (low ppt) permit monitoring of no more than four mass peaks for a single
sample injection, even with the sophisticated step-scan techniques developed in
Brehm Laboratory. In this instance, however, the level of TCDD's (40 ppm) in
*As previously noted, DDE is a degradation product of the pesticide DDT
162
-------
Figure 46. Mass fragmentograms using GC-MS-30 of mixtures
of 2,3,7,8-TCDD with other chlorinated compounds.
163
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sample 2 was very high and it was feasible to obtain an actual mass spectral scan as
this component of the sample eluted from the gas chromatograph.
Therefore, the MS-30 Mass Spectrometer was set up in the normal magnetic
scanning mode, and an aliquot of the extract of sample 2 was injected into the GC.
At the appropriate retention time, the mass spectrum of the eluted component was
scanned. Before this, we obtained similar mass spectra of a solution containing 10
ng of authentic 2,3,7,8-TCDD standard and of a solvent blank (benzene). The
instrumental parameters applicable to the scans are as follows:
Scan rate: 10 sec/decade, beginning 190 sec.
after sample injection
Mass range of scan: m/e 130 to m/e 350
Mass resolution: 1:1000
GC retention time for TCDD: 195 sec.
Other parameters: Same as described above
The relative intensities of the more prominent mass spectral peaks recorded in
these runs are listed in Table 30. The mass spectra obtained for the 2,3,7,8-TCDD
standard and for the extract of sample 2 are shown in Figures 47 and 48. These
spectra obviously agree quite well. There is no doubt that the unknown component
in sample 2 is a TCDD isomer and that it is present in a high concentration.
Apparently some components of the extract of sample 2, other than the TCDD's,
also contribute to m/e 194, 257, and 259, but these are not of concern here.
CONCLUSIONS AND RECOMMENDATIONS
As a means of assessing the levels of the extremely toxic TCDD's in process
streams, wastes, and sediments from the manufacture of chemicals, a method was
developed that proved to be applicable to about 70 percent of the industrial waste
sample types examined in this study. These sample types are typical of those that
would be collected in a routine chemical plant survey.
TABLE 30. RELATIVE INTENSITIES OF MAJOR IONS OBSERVED
IN MASS SPECTRAL SCANS
10 ng 10 iu.l of
2,3,7,8-TCDD EPA sample 2 extract
m/e standard Solvent blank (out of 2000 n\ total)
326 10 0 12
324 50 0 48
322 100 0 100
320 80 0 80
318 30 0 25
259 23 0 47
257 34 0 48
194 18 0 30
161 21 4 25
160 17 4 20
164
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-------
The analytical methodology implemented in this study is summarized in the
following five principal steps:
1. Preparation of a spiked and nonspiked aliquot of each sample in liquid
extractable form (organic phase),
2. A sample clean-up procedure that includes acid and base washes to remove
the bulk of the sample matrix.
3. An additional sample separation step using liquid chromatography.
4. Screening of samples for detectable levels of TCDD's with a low-resolution
GC-QMS system. This step is repeated with a spiked sample if positive
levels of TCDD's are detected.
5. Confirmation and quantification of the level of TCDD's by analysis of the
samples with a high-resolution GC-MS-30 system.
There are four major advantages with the implementation of this method:
1. The procedure offers a relatively rapid method for qualitative screening of
a wide variety of materials for possible contamination by TC D D's, through
the use of low-resolution mass spectrometry (GC-QMS showed a MDC of
I ppb or less in 50 percent of the samples).
2. Only samples in which the initial screening shows TCDD's need be
confirmed by use of GC with high-resolution mass spectrometry (minimum
resolution 1:10,000).
3. Analysis by high-resolution mass spectrometry yields extremely high
sensitivity as well as specificity. The need for both is indicated by the
finding of minimum detectable concentrations below 100 ppt in more than
half the samples tested.
4. The method warrants a high level of confidence owing to the use of an
internal standard and application of the four-ion monitoring technique.
Recovery of 37Cl4-2,3,7,8-TCDD from spiked samples indicates a
recovery range of 40 to 98 percent for the method. Further, by a procedure
in which the quantity of native-TCDD's detected is proportionately related
to the quantity of 37CU-2,3,7,8-TCDD added, the data may be
automatically corrected for recovery.
Although the procedures outlined here are acceptable for analysis of many
industrial process samples, they are not applicable to all sample types. Among
those examined in this study, the samples that could not be suitably analyzed are of
two types. First are those of biological origin, primarily wood and woodlike
products. It is probable that for such samples an acid digestion step is needed to
effectively destroy cellular walls and release any residue of TCDD's. Earlier work
at Brehm Laboratory on wood and other biological materials confirms the
effectiveness of such an approach.
The other type of sample not amenable to the method is more difficult to
characterize. Samples of this type formed emulsions in the preparation phase that
could not be resolved. Use of several common emulsion-breaking techniques such
as addition of excess solvent did not alleviate this problem. Unfortunately, owing
to the small number of samples of this type, no further information was obtained.
Additional work on such samples would be desirable.
Work should now be conducted toward the development and implementation of
the use of capillary columns in identifying each of the individual tetrachloro
isomers. This work would require that all of the 22 tetrachlorinated dibenzodioxins
be prepared in order to utilize them as standards.
167
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SECTION 5
ROUTES OF HUMAN EXPOSURE
The toxicity of some dioxins, especially 2,3,7,8-TCDD, has been demonstrated
in a number of incidents of human exposure. The most serious incidents, including
one man-made disaster, have affected the general public; these incidents have
resulted from industrial accidents, improper disposition of industrial wastes, and a
variety of other exposure routes. In addition to exposures of the general public,
human contact with dioxins has occurred in chemical manufacturing plants and in
other locations because of the occupational handling of these materials. This report
section summarizes both the reported incidents of human exposure to dioxins and
the potential exposure routes.
PUBLIC EXPOSURE
Industrial Accidents
The clearest demonstration of dioxin toxicity was a disastrous incident that
occurred on July 10, 1976, in Meda, Italy, at a plant producing 2,4,5-TCP for the
manufacture of hexachlorophene. The plant was operated by the Industrie
Chemiche Meda Societa, Anonima, (ICMESA), an Italian firm owned by the
Swiss company Givaudan, which in turn is owned by Hoffman-LaRoche, a Swiss
pharmaceutical manufacturer. The incident often is described inappropriately as
an explosion. A safety disc on an over-pressured 2,4,5-TCP reactor ruptured, and a
safety valve opened, releasing the reactor contents directly to the atmosphere
(Hombergeretal. 1979; Peterson 1978). The quantity of TCDD's released has been
estimated to be from 300 g to 130 kg (despite extensive study, there is still no
agreement as to the most likely amount) (Bonaccorsi, Fanelli, and Tognoni 1978;
Carreri 1978).
The incident occurred late on a Saturday afternoon. It resulted from the closing
of a valve that supplied cooling water to the reactor jacket. In the manufacturing
process, caustic soda had been used to hydrolyze 1,2,4,5-tetrachlorobenzene in a
solvent of ethylene glycol. After the mixture was heated, cooling water was turned
onto the jacket and should have remained on until the reaction was complete. A
decision had been made to postpone the next operation, a distillation to remove
ethylene glycol, until the following Monday. During the standby shutdown
procedures the cooling water valve apparently was closed inadvertently. Since the
reaction was incomplete, temperature and pressure continued to increase until the
limiting pressure of the safety devices was reached. When the release occurred, the
regular operators were not in the plant. Five minutes after the release started,
someone opened the cooling water valve and the influx of cooling water began to
slow down the reaction. Within 15 minutes, release of chemicals to the atmosphere
had stopped.
A slight breeze carried the toxic cloud over parts of 11 towns and villages, as
condensed chemicals fell from the cloud like snow. The town most affected was
Seveso, whose corporate limits adjoin the plant grounds. No emergency action was
taken by plant personnel or local authorities, although several people reported to
hospitals with chemical burns. Not until the next day, Sunday, was the mayor of
Seveso notified of the accident, and officials of other affected towns were not told
until Monday. The plant resumed normal operations Monday morning. No official
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emergency decree was issued until 5 days after the accident, and the possible
presence of 2,3,7,8-TCDD was not announced to the local population until after 8
days (Carreri 1978). By then, hundreds of animals had sickened and died, and
people with chloracne, principally children, were being hospitalized. Dow
Chemical Company has asserted that these deaths probably were due to
chlorophenol exposure (Crummett 1980). The plant workers went out on strike,
finally closing the plant. Since ICMESA had no suitable laboratory, samples of the
contamination had to be sent to Switzerland for analysis; not until 10 days after the
accident did Givaudan and Hoffman-LaRoche confirm that the contamination
was 2,3,7,8-TCDD. Only then were organized steps taken to assess the damage and
to safeguard the health of the people who had been exposed (Reggiani 1977;
Peterson 1978; Bonaccorsi, Fanelli, and Tognoni 1978; Carreri 1978).
It was discovered that most of the dioxin had fallen in a narrow strip extending
for about 5 km to the southeast from the plant (see Figure 49). The most heavily
contaminated area of 267 acres was designated Zone A, and was further divided
into seven numbered subzones corresponding to the relative degrees of
contamination. The population of Zone A was evacuated. A less contaminated
area of 665 acres was designated Zone B; official evacuation of this zone was not
ordered. A much larger area was designated Zone R (Respect or Risk), in which
dioxin contamination was judged to be too slight to be harmful.
ICMESA
IN
Figure 49. Map of Seveso area showing zones of contamination (A and B)
and zone of respect (R).
Source: Adapted from Fanelli et al 1980.
169
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Chloracne began to appear about 2 days after the accident. Within 6 days, 12
children were hospitalized; within 8 days, there were 14 (Parks 1978). Those first
affected were the most seriously affected, and some were still undergoing treatment
3 years after the incident (Revzin 1979). A screening of more than 32,000 children
of school age in the Seveso region resulted in the discovery of 187 cases of chloracne
(Hay 1978b). Officially, there were 135 confirmed cases within the first year, with
"new" waves of the skin disease appearing 18 and 24 months after the accident
(Bonaccorsi, Fanelli, and Tognoni 1978). Hoffman-LaRoche reported that most
chloracne was of "mild severity and quick recovery" and that there was no increase
in the susceptibility of the children to infectious disease (Reggiani 1979a). Only a
small percentage of those affected were adults.
Since 2,3,7,8-TCDD had been shown to cause birth defects and spontaneous
abortions in laboratory animals, the incidence of birth problems in the affected
population was studied. At present, the resulting data are inconclusive and
controversial, in part because of poor statistical data from prior years (Toxic
Materials News 1979c). Through May 1977, the spontaneous abortion rate for the
entire Lombardy region of Italy, which includes the Seveso area, was lower than
the worldwide frequency (15 percent versus 20 to 25 percent) (Reggiani 1977). A
private organization, however, reported that 146 malformed infants were born
during 1978 in the Seveso area, almost 3 times the number reported officially
(Chemical Week 1979b; Revzin 1979).
Four years after the ICMESA incident, the people of Seveso are resuming an
almost normal life. Hoffman-LaRoche has bought some of the heavily
contaminated properties near the plant and has enclosed them and the plant within
a tall plastic fence. Contaminated debris and soil from other locations, including
the carcasses of 35,000 animals that died or were slaughtered (Parks 1978) have
been dumped in the enclosure, and this area is now believed to contain 80 percent of
all the dioxin that was released (Chemical Week 1979h). Some nearby houses have
been decontaminated by removing the tile roofs, vacuuming and scrubbing the
walls with detergents and solvents, and clearing the grounds around them (Parks
1978). All the former residents have been allowed to return to their homes. Having
decided the danger is over, many no longer practice any safety precautions (Revzin
1979). None of the many proposals for decontaminating the plant property has
satisfied everyone; the situation not only poses a massive technical problem, but is
clouded with legal and political difficulties.
The Seveso incident has been called an environmental calamity (Parks 1978),
and the release of dioxins has been compared to an escape of nuclear radiation in its
potential for disaster (Revzin 1979). The effects of the 20-minute release on July 10,
1976, are still continuing and will not be known for years, perhaps not for
generations (Bonaccorsi, Fanelli, and Tognoni 1978). Although no human deaths
have resulted from the incident thus far, in the light of present toxicological
knowledge, late effects can be expected (Peterson 1978). Operations at the
ICMESA plant have not resumed since the 1976 accident (Watkins 1979b).
Contaminated Industrial Wastes
Manufacture of organic chemicals creates wastes, some of which may contain
dioxins. In one recorded incident a chemical plant waste known to contain a dioxin
has been clearly responsible for illness of a person not associated with chemical
handling operations (Beale et al. 1977). Other instances have been recorded and
continue to be discovered in which dioxins have been or are being discarded with
wastes in a manner that brings them into contact with the general public. This
report section lists the known examples of dioxin contamination of public land, air,
and water from disposal of industrial wastes. All are associated with present or
former producers of 2,4,5-TCP.
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Contained or Land/tiled Wastes—
The most concentrated waste sources of dioxins are the anhydrous liquids, tars,
and slurries, which 2,4,5-TCP manufacturers may discard by burying them in the
ground or by storing them in drums. These materials are handled both by personnel
of the manufacturing company and by contractors responsible to the
manufacturer.
The most notable incident of nonoccupational exposure to dioxin-contaminated
wastes of this type involved the spraying of waste oils containing TCDD's on horse
arenas and a private road in east-central Missouri in 1971 (Shea and Lindler 1975;
Environmental Protection Agency 1975b; Commoner and Scott 1976a; World
Health Organization 1977; Kimbrough et al. 1977). The wastes were traced to a
plant of the North Eastern Pharmaceutical Co. (NEPACCO) in Verona, Missouri,
which manufactured 2,4,5-TCP at that time. The residues of a distillation phase of
the process were stored above ground in a 7500-gallon tank. Periodically,
NEPACCO would contract with someone to dispose of the wastes. Between
February and October of 1971, the Bliss Salvage Oil Company held this contract
and during these 8 months hauled away 16,000 gallons. Presumably, most was
incinerated. In May and June, however, waste oils mixed with these distillation
residues were sprayed to control dusts on four horse arenas and a road on a farm
owned by the operator of the oil salvage company.
Unexplained deaths of animals occurred for almost 2 years. By December 1973,
over 60 horses had died in the arenas and over 40 had become ill (Commoner and
Scott 1976; Kimbrough et al. 1977). Many cats, dogs, rodents, birds, and insects
had also died. Seven people developed various disorders as a result of exposure. A
six-year-old girl who played regularly on an arena floor was most seriously
affected; she was treated for inflammation of the kidneys and hemorrhaging of the
bladder, along with other symptoms (Beale et al. 1977). She lost 50 percent of her
body weight over the course of the illness, but has since recovered.
Finally, the most heavily contaminated soil was removed from the arenas and
replaced. This apparently solved the problem, since no further incidents have been
reported. The soil, probably still containing dioxins, is now buried in a landfill and
under a concrete highway that was being built at the time (Commoner and Scott
1976a).
In Australia, Union Carbide of Australia Limited (UCAL), previously a
manufacturer of 2,4,5-TCP and 2,4,5-T, disposed of dioxin-contaminated wastes
by landfilling during the years between 1949 and 1971 (Chemical Week 1978b;
Dickson 1978). At the time these wastes were buried, landfilling was the most
acceptable method of disposal. It has been estimated that 16 to 30 kg of dioxins
may be present in the buried wastes (Chemical Week 1978b; Dickson 1978;
Chemical Week 1978c). In 1969, when dioxin contaminants in 2,4,5-
trichlorophenol were being publicized, UCAL began removing the dioxins by
adsorption onto activated carbon. The dioxin-contaminated carbon, now stored in
steel drums, presents a disposal problem (Dickson 1978).
Dioxins have been found in two chemical landfills in Niagara Falls, New York.
One of these, the Love Canal, is now the site of a residential community, including a
school. The landfill previously was used by the Hooker Chemical Company for
burying chemical wastes, including those from the manufacture of 2,4,5-TCP. A
rising water table has brought the chemicals to the surface (Chem. and Eng. News
1978). Approximately 80 different chemicals have been identified, including a
number of known carcinogens (Cincinnati Enquirer 1978a). Recently it was
reported that TCDD's were found at the site (Chemical Week 1979a; Wright State
University 1979a, 1979b). About 30 tons of 2,4,5-TCP wastes are buried in the Love
Canal. Hyde Park, a larger toxic landfill used by Hooker, also has yielded positive
analyses. Environmental evaluations of three plants located near the landfill found
TCDD's in dust from these plants and in water samples taken from sediments in a
nearby creek (Chemical Regulation Reporter 1980).
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One of the largest accumulated quantities of dioxin-contaminated anhydrous
wastes now known is a cache of approximately 3000 drums of chemicals found in
1979 at the Vertac plant in Jacksonville, Arkansas (Fadiman 1979). The proper
procedure for final disposition of this material, which may contain as much as 40
ppm or more TCDD's, has not been determined. (See Sections 4 and 8 of this
report.)
Incinerated Wastes—
A number of present and previous producers of 2,4,5-TCP and 2,4,5-Tdisposed
of wastes by incineration. This method is used by the Dow Chemical Company and
was once used by the ICMESA plant and by NEPACCO, which discarded its
wastes through a contract incineration company. A recent report has raised a
significant question as to whether past or present incineration methods destroy all
dioxins. Dow reported in 1978 that fly ash from both stationary tar and rotary kiln
incinerators contains low concentrations of dioxins, even that from incinerators
designed to burn chemical wastes (Dow Chemical Company 1978). TCDD's bound
to particulate matter are largely unaffected by even high-temperature incineration
(Rawls 1979; Ciaccio 1979; Miller 1979).
It has been suggested that incineration of dioxin-contaminated chemical wastes
is primarily responsible for the observed presence of TCDD's in and around the
Dow plant in Midland, Michigan (Merenda 1979; Ciaccio 1979).* If this is shown
to be the case, pollution of the atmosphere from chemical incinerators may be an
important route in the exposure of the public to dioxin chemicals. Miller (1979) has
suggested that a worldwide background of atmospheric dioxin contamination may
exist as a result of the incineration by the U.S. Air Force of 10,400 metric tons of
Herbicide Orange containing up to 47 ppm TCDD's (see Ackerman et al. 1978).
This operation took place in the Pacific in 1977. Although there are no data that
confirm the presence of widespread atmospheric pollution from this source,
TCDD's were detected in some stack emission samples (Tiernan et al. 1979).
Discharged Water Wastes—
Dioxin concentrations that exceed theoretical solubility limits (Crummett and
Stehl 1973) may occur in industrial wastewaters because of 1) the presence of other
organic materials in the wastewater that would tend to increase the solubility of the
dioxin, and/or 2) the presence of suspended solids to which the dioxins are
adsorbed. In either event, it is possible that low levels of dioxins may be carried
routinely into the environment by industrial effluents, especially those associated
with the production of chlorophenols. Dow has asserted that low levels of dioxins
may also be associated with paniculate matter leaked to the sewer from scrubbers
on powerhouses and incinerators (Crummett 1980).
Little published information addresses the question of dioxins in such industrial
water effluents. A 1978 report from Dow Chemical Company contends that their
pesticide plant effluent discharges were not responsible for the dioxins found in a
number of Tittabawassee River fish, collected downstream from the Dow
discharge. The report states that dioxins are formed during any combustion
process and therefore may be found everywhere in the environment. In late
communications, Dow indicates that dioxins indeed have been found above the
Dow effluent outfall by Dr. David Stallings of the U.S. Department of Interior and
the Michigan Department of Natural Resources (Crummett 1980).
Other data presented in the Dow report indicate that particulates in scrubber
water contained 46 ppb TCDD's, 200 ppb hexa-CDD's, 970 ppb hepta-CDD's, and
120 ppb OCDD. The water was used to scrub the gas stream from a rotary kiln
incinerator fired with a supplemental fuel to burn chemical wastes. Disposition of
*Dow believes that the observed presence of TCDD's and other dioxins in Midland and other metro-
politan areas is due not only to chemical incinerators but to various other combustion sources such as
powerhouses, diesel engines, charcoal grills, etc (Dow Chemical Company 1978, Rawls 1979)
172
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the overflow from the scrubber is unknown; however, it is unlikely that any water
treatment system can consistently remove 100 percent of a low-level constituent
such as TCDD's, especially if a portion of the TCDD's are adsorbed to paniculate
matter.
In 1976, analysis of effluent water from the Vertac plant in Jacksonville,
Arkansas, showed 0.2 to 0.6 ppb of TCDD's (Sidwell 1976a). In contrast, analysis
of effluent from the city stabilization ponds, to which the plant effluent was sent,
showed no TCDD's (Sidwell 1976b). Because no detection limits were reported, the
presence of TCDD's in low concentration in the stabilization pond effluent
remained a possibility. There was also a question of the validity of the analytical
method used in the latter examination.
Chemists at Wright State University have recently reported on the analysis of
100 process and environmental samples taken by the U.S. EPA from the Vertac site
and surrounding area (Tiernan et al. 1980). TCDD's were detected in many of the
samples at ppt to ppb levels. Composite samples of soil and water from the city
sewage treatment plant lagoon contained 8 ppb TCDD's. Bottom core samples
from the Vertac cooling pond contained 2 to 102 ppb TCDD's; however, no
TCDD's were detected in the cooling pond discharge sample (detection limit of
0.05 ppb). Similarly, liquid discharge samples (2) from the equilization basin con-
tained no detectable TCDD's (detection limit 0.010 ppb), even though a bottom
mud sample from the basin contained about 400 ppb TCDD's.
Treatment of wastes at PCP production plants and wood treatment plants is
usually accomplished by oxidation ponds, lagoons, or spray irrigation. The
efficiency of these treatment schemes has not yet been evaluated where dioxins are
concerned. There is evidence, however, that water-mediated evaporation is at least
partly responsible for the removal of chlorophenols (and also possibly dioxins)
from oxidation ponds (Salkinoja-Salonen 1979b). Insufficient treatment could
result in contamination of waterways and thus in potential public exposure.
Transportation Accidents
In January 1979, the derailment of a tank car of orthochlorophenol in Sturgeon,
Missouri, resulted in symptoms of chloracne in a cleanup worker. Analysis of the
tank car contents showed less than 0.1 percent trichlorophenol contamination and
also 37 ppb TCDD's. Subsequent analyses by the EPA confirmed that the dioxin
contamination was 2,3,7,8-TCDD (Chemical Week 1979d and 1979e; Poole 1979).
Further details of the incident have not been released because of extensive legal
actions now pending involving the residents of the town and employees of the
manufacturing, transportation, and contract clean-up companies.
Although the incident at Sturgeon is the only one reported in which dioxins were
identified, it is especially significant because of the nature of the chemical involved.
The manufacture of orthochlorophenol offers no direct chemical pathway to the
side reactions that form 2,3,7,8-TCDD. Nevertheless, contamination with this
most-toxic dioxin was present. Product distillation is at least a hypothetical origin.
Continuing examinations of the source of the 2,3,7,8-TCDD are indicated and are
being conducted.
Herbicide Applications
For many years, herbicides made from dioxin-contaminated 2,4,5-TCP were
widely distributed into the environment. Since the herbicides were less toxic to
grasses, canes, and established trees than to broadleaf weeds and undergrowth
plants, they found wide application wherever the objective was to stimulate growth
of the more resistant plants. The applications included residential lawns; right-of-
ways for power lines, railroads, and highways; forest lands intended for future
lumbering; pasturelands; and food crops such as rice and sugar cane. Regulatory
and environmental actions have now halted most of these uses of chemicals that
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may contain dioxins, but a number of public health incidents have been associated
with herbicide applications.
In Oregon, application of 2,4,5-T and silvex by timber companies and the
government to forest areas has brought charges of increased incidences of
miscarriage by women living near the sprayed areas (American Broadcasting
Company 1978; WGBH Educational Foundation 1979). It is claimed that among 8
of the women, 11 miscarriages occurred within 1 month after herbicide
applications. The EPA investigated these charges and found sufficient evidence of
danger of the public health in sprayed areas to place an emergency ban on
continued use of 2,4,5-T and silvex in these and other areas (Blum 1979). Other
incidents in Oregon involved several people who complained of illness after
herbicide sprayings (WGBH 1979). Abortions among cows and deer, and the
deaths of fish, quail, and grouse were also reported to be associated with the
sprayings (WGBH 1979). An allergist specializing in environmental medicine
reported that the complaints of diarrhea and recurrent boils among the exposed
people could have been caused by a dioxin contaminant in the herbicides
(Anderson 1978).
In northeastern Minnesota, a family reported that offspring of pigs, chickens,
and rabbits that had fed in areas sprayed by a U.S. Forest Service helicopter were
born deformed, or later developed deformities (ABC News 1978; Anderson 1978;
Cincinnati Enquirer 1978c). For over 5 months after the spraying, the family
complained of intense bellyaches, headaches, fever, nausea, diarrhea, and
convulsions. An analysis of the family's water supply by the Minnesota health
authorities revealed traces of a herbicide that contained 2,4-D, and 2,4,5-T. The
presence of dioxins was not reported.
Another source of concern is the possible effects of the massive applications of
Herbicide Orange in Vietnam. Reports from some researchers indicate that
numerous deformities have been found in children 6 to 14 years old (Young et al.
1978). Some reports also state that spontaneous abortions among women in
sprayed areas were not uncommon, and that some people died as a result of the
spraying. It has been estimated that at least 25,000 children in South Vietnam could
be assumed to have acquired hereditary defects from this cause (Young etal. 1978).
Others claim that these reports are virtually impossible to validate. The National
Academy of Sciences concluded from their studies that there was no consistent
correlation between exposure to herbicides and birth defects (Young et al. 1978).
In 1969, citizens of Globe, Arizona, complained of human and animal illnesses
after the U.S. Forest Service had applied 3680 pounds of silvex and 120 pounds of
2,4,5-T to the nearby Kellner Canyon and Russell Gulch (Young etal. 1978). After
investigation by the Office of Science and Education and by the U.S. Department
of Agriculture, it was concluded that there were no significant effects on birds and
wildlife, there was no indication of illnesses in livestock greater than in other
regions, and human illnesses were those that commonly occur in the normal
population, except for one individual who developed skin rash and eye irritation
from cleaning out an empty herbicide drum.
In Swedish Lapland, two infants with congenital malformations were born to
women who had been exposed to phenoxy herbicides (Young et al. 1978). Medical
scientists could find no evidence to substantiate any conclusion beyond a
coincidental occurrence of the birth defects and the herbicide spraying.
In New Zealand, two women who had been exposed to 2,4,5-T during their
pregnancies gave birth to deformed babies (Young et al. 1978). In one case 2,4,5-T
was ruled out as the cause because although the mother had been exposed to the
herbicide during pregnancy, the exposure had occurred after the time in the
pregnancy when the deformity is known to usually occur. No conclusions were
reached on the other case.
Also in New Zealand, it was reported that deformities in infants occurred in three
areas of the country and that 2,4,5-T was suspected (Young et al. 1978). After an
174
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investigation, it was concluded that there was no evidence to implicate 2,4,5-T as
the cause of the deformities.
In Australia, skin rashes, respiratory problems, and higher incidences of birth
defects and infant mortality may be associated with 2,4,5-T sprayings and dioxin
contaminants (Chemical Week 1978d).
Although no published reports deal with the subject, large segments of the
suburban U.S. population are seasonally exposed to 2,4-D spray applications to
lawns for weed control. Until 1979, silvex was also a common constituent of many
of these formulations.
There is little published information relating to the use of 2,4,5-T in rice fields.
Rice is grown in Arkansas, Louisiana, and Texas, and possibly also in Mississippi,
usually in localized areas that include facilities for flooding of the fields (a
requirement in rice culture). Dioxins, including TCDD's could be accumulating in
the soil of these fields or in runoff channels. This appears to be a principal area of
missing information with respect to continued use of these herbicides. Dow
reportedly has published a study of fish living in rice-field irrigation water that has
been treated with 2,4,5-T (Shadoff et al. 1977b).
Foods
A number of human food sources have been found to be contaminated with
TCDD's. Three different research teams have reported finding dioxins in the fat of
cattle that had grazed on pasture experimentally treated with 2,4,5-T(Meselson, O'
Keefe, and Baughman 1978; Kocher et al. 1978; Solch et al. 1978, 1980). Levels
reported ranged from 4 to 15 ppt and 12 to 70 ppt, and 10 to 54 ppt, respectively. In
contrast, however, samples from cattle fed ronnel contaminated with TCDD's
showed no dioxins at a detection limit of 10 ppt (Shadoff 1977). TCDD's have been
found at levels ranging from 14 to 1020 ppt in fish and crustaceans collected in
South Vietnam (Baughman and Meselson 1973). Fanellietal.(1980b)andCocucci
et al. (1979) found TCDD's in locally grown garden vegetables, fruit, and dairy
milk supplies following the ICMESA accident in Italy in 1976. An investigator
analyzed human milk samples collected in 1970 during the herbicide operations in
South Vietnam, and found that they were contaminated with 40 to 50 ppt TCDD's
(Baughman 1974). He reported that the mothers could have been contaminated
either by direct exposure or by ingestion of contaminated foods. About 1 ppt
TCDD's has been reported in breast milk from U.S. mothers living near pasture
land (Meselson, O'Keefe, and Baughman 1978); however, a subsequent study of
103 samples of breast milk from mothers living in sprayed areas revealed no
TCDD's at a detection limit of 1 to 4 ppt (Chemical Regulation Reporter 1980b). In
1973, TCDD's were detected in several U.S. commercial fatty acids (Firestone
1973).
Other chlorinated dioxins have also been detected in foods. Tiernan and Taylor
(1978) found hexa-, hepta- , and/or OCDD in 19 of 189 USD A beef fat samples at
levels in excess of 0.1 ppb.
Firestone reported finding hexa-CDD's, hepta-CDD's, and OCDD in gelatin
samples obtained from supermarkets and in bulk gelatin (Firestone 1977). Gelatin
is a byproduct of the leather-tanning industry, which routinely used PCP and TCP
as preservatives (U.S. Environmental Protection Agency 1978b). Total United
States comsumption of gelatin is estimated at 32 million kilograms per year, of
which 20 percent is imported. In this study, dioxins occurred in 14 of 15 commercial
gelatin samples at levels ranging from 0.1 to 28 ppb total dioxins.
Pentachlorophenol was also identified in most samples. 2,3,7,8-TCDD was not
detected in any sample. These data are presented in Table 31.
Analysis by Dow Chemical Company of fish from the Tittabawassee River,
which receives the effluent from their Midland complex, revealed the presence of
TCDD's, hexa-CDD's, and OCDD in trace quantities (Dow Chemical Company
175
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TABLE 31. DIOXINS IN COMMERCIAL GELATIN3
Dioxins (ppb)b
Sample no.
1
2
3
4
5
6
7
8
9
(continued)
Sample identity
Bulk domestic pork skin
gelatin
Bulk domestic pork skin
gelatin
1975 Consumer package
(Texas)
1975 Consumer package
(Texas)
1977 Consumer package
(Washington, D C )
1977 Consumer package
(Washington, D C )
1977 Consumer package
(Washington, D C )
Imported bulk gelatin
(Columbia, South America)
Imported bulk gelatm-A
(Mexico)
PCP 1,2,4,6,7,9 1,2,3,6,7,9
(ppm) hexa-CDD's hexa-CDD's
00 0 00 0 00
00 0 00 0 00
38 0 00 0 20
64 0 00 0 20
N A c 0 00 0 00
N A 0 03 0 20
NA 010 070
001 000 000
35 002,003 030,030
1,2,3.6,7,8
hexa-CDD's
0.00
000
0.00
000
0.00
003
040
000
0 40,0 60
1,2,3,7,8,9
hexa-CDD's
000
000
003
004
000
005
009
000
005,002
1,2,3,4,6,7,9
hepta-CDD's
0.01
000
000
000
002
020
080
020
3 80,3 90
1,2,3,4,6,7,8
hepta-CDD's OCDD
0.00 0 1
0.00 0.0
0 10 02
030 04
002 01
016 02
080 06
020 06
460,5.30 20,16
Total
Dioxins
0.1
00
06
1 0
02
08
36
09
30,26
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TABLE 31. (continued)
Sample no. Sample identity
Dioxins (ppb)
PCP 1,2,4,6,7.9 1,2,3,6,7,9 1,2,3.6,7,8 1,2,3,7,8,9 1,2,3,4,6.7,9 1,2,3.4,6,7,8 Total
(ppm) hexa-CDD's hexa-CDD's hexa-CDD's hexa-CDD's hepta-CDD's hepta-CDD's OCDD Dioxins
10 Imported bulk gelatm-A
(Mexico)
11 Imported bulk gelatin-A
(Mexico)
12 Imported bulk gelatm-B
(Mexico)
13 Commercial blend
(67% domestic pork skin
gelatin, 33% Mexican-A)
14 Commercial blend
(65% domestic pork skin
gelatin, 35% Mexican-A)
15 Commercial blend
(91% domestic pork skin
gelatin, 9% Mexican-A)
7.5 0.02,0.02 0.10,010 0.30,0.20 0.05,009 250,2.70 2.80,2.90 20,17 25,23
8.3 0.02,0.02 020,040 0.60,0.80 0.07,020 3.50,400 3.60,5.00 21,18 29,28
0.3 000,000 0.00,0.00 000,000 000,000 002,002 0.02,002 01,01 0.1,01
22 001,001 0.06,008 020,0.30 0.02,009 0.90,0.90 1.20,1.20 48,43 70,69
31 001,001 0.05,008 010,0.20 002,007
0.60,0.50
060,080 29,1.9 38,36
10 001,001 0.02,003 004,0.09 001,0.02 0.20,0.30 030,040 1.4,1.1 20,20
a—Source Firestone 1977
b—Limits of quantitation were about 0 006, 0 012. and 0 018 ppb for the hexa-CDD's, hepta-CDD's, and OCDD, respectively, using electron-capture gas-liquid chromatography
c—N A = Not analyzed
-------
1978). Catfish from the Saginaw Bay contained 0.024 ppb TCDD. Michigan health
authorities have found TCDD's in fish from the Flint, Cass, and Shiawassee
Rivers. Dow has pointed out that these three rivers have huge combustion sources
on their banks but no pesticide plants (Crummett 1980). The Food and Drug
Administration has recommended that Michigan set a maximum residue level for
dioxins in fish at 100 ppt (Toxic Materials News 1979e).
TCDD's have been recently detected in leather meal, although in unquantified
amounts (U.S. Environmental Protection Agency 1978b). Like gelatin, leather
meal is a byproduct of the leather-tanning industry. It is reported that the FDA
permits up to 1 percent leather meal in swine food diets, but this level is believed to
be too restrictive to be economically advantageous. Poultry feeding tests have
indicated that 6 percent leather meal in the diet could be economically
advantageous if the leather meal were free of dioxins. EPA recently withdrew an
application to FDA for approval of the inclusion of leather meal in poultry feed
because of the discovery of TCDD's in the meal.
There is no published information relating to the residual level of TCDD's on
harvested rice crops that have been treated with the herbicide 2,4,5-T.
Pentachlorophenol has been found in dairy products, grains, cereals, root
vegetables, fruits, and sugars (U.S. Environmental Protection Agency 1978e).
Water Supplies
Another apparent gap in information concerns drinking water. There are no
published reports of studies that searched specifically for dioxins in surface or well
waters used for drinking-water supplies. A report from the National Academy of
Sciences (1977) indicates that there are no reports of dioxins in drinking water, but
does not indicate clearly whether dioxins have not been detected, or whether no
research has been conducted. Dr. James Allen of the University of Wisconsin
reported in 1978 that dioxins have been detected in Great Lakes waters, but
apparently no data to this effect have been published.
In 1978, Dow Chemical Company reported that their analysts were unable to
detect 2,3,7,8-TCDD in two surface water samples taken from the Tittabawassee
River near Dow's Midland plant. The detection limit cited was 0.001 ppb.
It is possible that even if toxic chlorodioxins are not present in surface waters,
they might be formed at low levels during purification of public water supplies.
Early research with unsubstituted dioxins showed that chlorinated dioxins could
be formed from the unsubstituted dioxin by direct chlorination (Oilman and
Dietrich 1957). Although no tests of this possibility have been reported, any dioxin
entering a municipal drinking water system may become chlorinated during
routine chlorine disinfection processes, and thus its toxicity could be greatly
increased.
Combustion Residues
The presence of dioxins in fly ash from municipal incinerators is described in
Section 3. Tests by Dow Chemical Company that found dioxins in fireplace soot
and other combustion processes are also described elsewhere in the report. Here it
is emphasized that these observations identify another source of exposure of the
public to dioxins. To date, the available data are insufficient to allow definition of
the relative importance of nonpesticide combustion as a contributor to dioxin
pollution of the environment.
Miscellaneous Pesticide Uses
In addition to their principal uses as a raw material and an agricultural pesticide,
2,4,5-TCP and other chlorophenols that may contain dioxins are brought into
contact with the public in other ways. One such use is in disinfectants (U.S.
178
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Environmental Protection Agency 1978i). These are used on suri'aces ot swimming
pools, household and hospital sickroom equipment, food processing plants and
equipment, and hospital rooms, as well as on surfaces that contact food. They are
also used in bathrooms and restrooms, on shower stalls, urinals, floors, and toilet
bowls. Another minor use is as a constituent of metal cutting fluids. It is not known
whether any of these cutting fluids are sold commercially.
Commercial products containing pentachlorophenol are readily available to the
public. Examples of such products are paints containing PCP as a fungicide or
preservative, and formulations for wood preserving. The latter typically contain
about 4 percent PCP. Exposure of the users of PCP products is most likely to occur
during use. In one reported case, however, a woman became weak and lost 20
pounds over a 3-month period that followed the application of paint containing
PCP to interior paneling. Chronic inhalation of the PCP vapors from the walls was
said to be the cause (U.S. Environmental Protection Agency 1978e).
Dermal absorption of sodium pentachlorophenate (Na-PCP) resulted in the
illness of nine newborn infants and the subsequent death of two (U.S.
Environmental Protection Agency 1978e). This exposure occurred in a hospital
after clothing and linens were accidentally washed with Na-PCP. Analysis of
clothing and bed linens showed PCP residues ranging from 2.64 to 195.0 mg/100 g.
Analysis for dioxins was not reported.
Since many wood products are treated with PCP, exposure could occur by
excessive handling or contact. Items such as telephone posts, fence posts, and
similar products, readily accessible to the public, could present health hazards if
subsequently handled.
Hexachlorophene Exposures
Until 1972 hexachlorophene was widely used as a bacteriostatic agent in many
commercially available products. Hexachlorophene is made from 2,4,5-TCP, a
known dioxin source. In September 1972 the FDA began requiring new drug
applications for all drugs containing 0.75 percent or more hexachlorophene and
also required that these drugs be made available only by prescription. Products
containing 0.1 percent hexachlorophene as a preservative are not subject to the
prescription requirement and are still marketed commercially.
Hexachlorophene for use in drug and cosmetic products is apparently made
from purified 2,4,5-trichlorophenol. The dioxin content of currently marketed
hexachlorophene is believed to be less than 15 /ug/kg (15 ppb) (World Health
Organization 1977). There apparently are no published references that report
positive analyses of dioxins in hexachlorophene.
Sickness and death resulting from exposure to hexachlorophene have been
reported, occurring primarily among children and infants (Kimbrough 1976; U.S.
National Institute of Environmental Health Sciences 1978). It is not known
whether dioxin contaminants are responsible. In one incident, four children died
following exposure to a detergent containing 3 percent hexachlorophene
(Kimbrough 1976). In 1972,41 infants and children died and a much larger number
became ill after being exposed to baby powder to which excessive quantities of
hexachlorophene had been added accidentally (Kimbrough 1976). The
hexachlorophene concentration in the baby powder was 6 percent.
A Swedish study concerned children born to mothers who were nurses in
hospitals and who had been exposed to hexachlorophene soap in early pregnancy;
among 65 children, 11 malformations were found, 5 of which were severe (U.S.
National Institute of Environmental Health Sciences 1978). Out of 68 children
born to unexposed mothers, only one slight malformation was observed.
179
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OCCUPATIONAL EXPOSURE
Except for the 1976 disaster at Seveso, most clearly recognized human injuries
associated with dioxins have been suffered by persons who came into contact with
the chemicals as a result of their occupation. The most directly affected probably
would be workers in plants of the chemical manufacturing industry where the
dioxins are created. Other industries and activities, however, also use dioxin-
contaminated chemical products and thus represent another source of worker
exposure (for purposes of this report, the exposure of Vietnam military personnel
to dioxins is considered occupational). Still other occupational exposures result
from work in analytical or research laboratories and from handling of chemical
wastes. This report section describes the reported incidents and the potential for
human exposure due to occupational activities.
A large-scale study of occupational exposure to dioxins is now underway by the
National Institute for Occupational Safety and Health (NIOSH). With
cooperation from the chemical industry, major unions, and the Department of
Defense, NIOSH is compiling a registry of the population of chemical workers in
the United States who have had documented exposure to 2,3,7,8-TCDD, either in
the manufacture of herbicides or in industrial accidents. Once this registry has been
developed, NIOSH plans to evaluate trends in mortality of the exposed workers
and, if the data permit, will consider conducting studies of morbidity and
reproductive effects (Robbins 1979).
The NIOSH program will augment similar studies in progress in connection with
present and former workers exposed to dioxins in Jacksonville, Arkansas, and
Nitro, West Virginia (Occupational Safety and Health Reporter 1979).
Chemical Manufacturing Industry
More than 200 dioxin-related industrial accidents occurred around the world
during the 30 years prior to 1979 (American Industrial Hygiene Association
Journal 1980). The following paragraphs represent only a sampling of these
incidents, most of which involve the manufacture of 2,4,5-TCP. Table 32
summarizes some of the other incidents not described in detail. Table 33 is a
sampling of the incidents involving plant accidents.
The earliest major incident was an explosion in 1949 at a plant of the Monsanto
Company in Nitro, West Virginia. This plant operated from 1948 to 1969, and the
explosion was reported to have affected 228 people (Whiteside 1977; Young et al.
1978). The symptoms included melanosis, muscular aches, nervousness, and
intolerance to cold, in addition to chloracne. A current occupational study of the
long-term effects of dioxin exposure is being conducted of 121 people who were
working in the plant at the time, including all of those who developed chloracne as a
result of the accident. Preliminary study reports indicate no excess deaths from
cancer or cardiovascular disease among these workers (American Industrial
Hygiene Association Journal 1980).
In 1953, an explosion occurred in Germany at the factory of Badischer Anilin
and Soda-Fabrik, which was producing 2,4,5-TCP by hydrolysis of 1,2,4,5-
tetrachlorobenzene with sodium hydroxide in a solvent of methanol (Goldmann
1972). Following the explosion the safety valves released vapors, which filled all
reactor rooms on all four floors of the plant. After a few minutes, vapors that had
not been withdrawn with exhause fans had condensed as solids on the apparatus,
walls, windows, and doors. Chloracne developed in 42 people, 21 of whom also
developed disorders of the central nervous system or internal organs. In addition, 5
years after the explosion a worker replacing a gasket on one of the reactors
developed several disorders a few days later; one year later the worker died.
An explosion at the TCP-producing factory of the Coalite and Chemicals
Products at Derbyshire, U.K., resulted in 79 workers contracting chloracne (May
1973).
180
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TABLE 32. REPORTED INCIDENTS OF OCCUPATIONAL EXPOSURE TO DIOXINS
DURING ROUTINE CHEMICAL MANUFACTURING3
Year
1949
1952
1952-53
1954
1956
1956
1960
1964
1964
1965-69
1970
1972
1973
1974
1975
Country
West Germany
West Germany
West Germany
West Germany
United States
United States
United States
U S.S.R
United States
Czechoslovakia
Japan
U.S.S.R
Austria
West Germany
United States
Number of
Manufacturer/ plant location Chemical produced persons exposed
N.A.VNordrhem, Westfallen
N.A./N A
Boehringer/N A.
Boehrmger, Ingelheim/Hamburg
Diamond Alkali/Newark, NJ
Hooker/N.Ac
Diamond Shamrock/N.A.c
N A/N A
Dow Chemical Company/Midland, Ml
Spolana/N.A.
N.A/N.A
N A./N.A.
Linz Nitrogen Works/N.A.
Bayer/Uerdmgen
Thompson Hayward/Kansas City, MO
PCP, TCP
TCP
TCP
TCP; 2,4,5-T
2,4-D; 2,4,5-T
TCP
TCP
2,4,5-T
2,4,5-T
TCP
PCP; 2,4,5-T
TCP
2,4,5-T
2,4,5-T
TCP
17
60
37
31
29
N.A.
N A.
128
60
78
25
1
50
5
N.A.
a—Adapted from Young et al 1978
b— N A = Not available.
c—Not known whether occupational exposure was involved in the incident
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TABLE 33. OCCUPATIONAL EXPOSURES TO DIOXINS THROUGH ACCIDENTS
IN THE CHEMICAL MANUFACTURING INDUSTRY3
Year
1949
1953
1956
1962
1963
1966
1968
1976
Country
United States
West Germany
France
Italy
Netherlands
France
United Kingdom
Italy
M anuf acturer/ locati on
Monsanto/Nitro, WV
BSAF/Ludwigshafer
Rhone Poulene/Grenoble
Philips-Duphar/Amsterdam
Rhone Poulene/Grenoble
Coalite and Chemicals Products/
Bolsover, Derbyshire
ICMESA/Meda
Product involved
TCP
TCP
2,4,5-T
TCP
TCP
TCP
TCP
TCP
TCP
Number of
workers affected
228
55
17
5
50
21
79
134b
a—Adapted from Young et al. 1978
b—These were not workers but local residents (124 children and 10 adults), no workers were reported affected
-------
Six months after an explosion in the Netherlands at the Philips-Duphar plant,
which was producing 2,4,5-TCP, 9 of 18 men working on decontaminating the
plant contracted chloracne (World Health Organization 1977).
During the Seveso incident, the public was more seriously affected, but the plant
workers were also exposed to dioxins. Reports are fragmentary and sometimes
conflicting. A company-sponsored report says that of the 10 workers in the plant at
the time of the accident, none, not even those who came in direct contact with the
reactor, showed signs of exposure; further, a year later, none of the plant workers
showed any signs of disease associated with dioxin toxicity (Reggiani 1977).
Another report states that one volunteer worker, after helping to clean out the
material that remained in the reactor after the accident, developed severe chloracne
(Parks 1978). Another report states that among 170 workers exposed to the
contamination, 12 developed chloracne, 29 developed liver disease, 17 developed
high blood pressure, and 20 others suffered from other various disorders (Zedda,
Cirla, and Sala 1976). Finally, another report states that 64.5 percent of 141 former
workers suffer from liver problems and others suffer from a variety of other
complaints; 79 of 160 workers involved in the cleanup campaign show
chromosomal abnormalities (Chemical Week 1978a).
Workers at the Vertac plant in Jacksonville, Arkansas may have been affected by
exposure to dioxins, even though no catastrophic event occurred during the many
years the plant produced 2,4,5-TCP. Graphic accounts of chloracne attacks in
plant workers appeared in an investigative article published in a nontechnical U.S.
magazine (Fadiman 1979). In June 1979, Arkansas health officials found signs of
chloracne in 13 of the 74 current Vertac employees (Richards 1979c). In July 1979,
a task force of medical experts began an intensive examination of about 150
present and former employees; no definitive conclusions have been reported.
Although not necessarily employees of chemical manufacturers, some workers
undergo occupational exposure to dioxins in the handling or transportation of
bulk chemicals outside of the plant. In one reported incident after the railway
derailment in Sturgeon, Missouri, low levels of 2,3,7,8-TCDD were found in the
blood of two of the cleanup workers (Chemical Week 1979d, 1979e, and 1979i;
Poole 1979; Taylor and Tiernan 1979). These were employees of a firm hired by the
railroad to clean up the spill.
In a similar incident in Sweden, railroad workers were exposed to 2,4-D and
2,4,5-T. A medical study concluded that these herbicides showed a possible tumor-
inducing effect (Young et al. 1978). The presence of dioxins apparently was not
considered in this study.
Use of Chemical Products
When makers of dioxin-contaminated products sell these products to other
industries or organizations, the personnel of these secondary users are subject to
occupational exposure to dioxins. Table 34 lists several related industries that
process or handle chemical products with a potential dioxin content.
It is estimated that 80 percent of all pentachlorophenol produced is used in
wood-treating operations (Arsenault 1976; American Wood Preservers Institute
1977; U.S. Environmental Protection Agency 1978e). Exposure in this secondary
industry may occur during the mixing of the PCP crystals and solvent (American
Wood Preservers Institute 1977). Many of the larger wood-treating operations now
use automatic closed mixing systems, which limit the chances for worker exposure.
Chloracne symptoms have developed, however, in workers in one wood-treating
plant; the exposures resulted from manual opening and dumping of bagged PCP
(U.S. Dept. HEW 1975). Workers also may be exposed to PCP by handling of
wood after treatment.
Other uses for pentachlorophenol and its sodium salt are in cooling tower water
treatments, in pulp and paper mills, and in tanneries (U.S. Environmental
183
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TABLE 34. INDUSTRIES USING DIOXIN-RELATED CHEMICALS
Industry
Chemical(s)
Process application
Textiles
Leather tanning
Wood preserving
TCP
TCP
PCP
Process water fungicide
Process water fungicides
Active ingredient in dip vat/
pressure treatment
Pulp and paper
TCP
PCP
Process water slimicide, fungicide
Pesticide formulators
and applicators
2,4,5-T
2,4-D
silvex
ronnel
erbon
hexachlorophene
Active ingredient formulated
or sprayed
Automotive
TCP
Metal cutting fluids, foundry core
washes
Miscellaneous industries TCP
Slimicide in cooling tower waters
Household and industrial TCP Active ingredient disinfectant
cleaning products hexachlorophene
Building/construction PCP
Termite control
Drug and cosmetics
hexachlorophene Product preservative or active
ingredient
Paint
TCP
PCP
Preservative/mi Idewcide
Farming (cattle)
2,4,5-T
2,4-D
Rangeland weed control
Railroad, telephone 2,4,5-T
(construction and silvex
maintenance) 2,4-D
Weed control on right-of-ways
184
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Protection Agency 1978e). Potential for worker exposure therefore exists in these
industries. Cooling tower waters from one 2,4,5-TCP facility have recently been
found to contain ppb levels of TCDD's (see Section 4 of this report).
People involved in the application of herbicides manufactured from or
formulated with 2,4,5-TCP and derivatives may be exposed to dioxin
contaminants. These include workers involved in aerial applications and those
employed by commercial lawn-care companies who apply phenoxy herbicides
manually.
Exposures to Herbicide Orange—
Thousands of military personnel were exposed during the Vietnam conflict to
Herbicide Orange; these exposures are currently the topic of considerable litigation
and are not outlined in detail in this report. The General Accounting Office (G AO)
notes that 4800 veterans have asked for treatment for exposure to Herbicide-
Orange (Toxic Materials News 1979d), and the suits are being brought against
former manufacturers, reported to include Dow Chemical Company, Hercules,
Diamond Shamrock, Monsanto, Northwest Industries, and North American
Philips (Chemical Week 1979c).
Summaries of the situation were published in Science (Holden 1979) and by the
New York Times (Severo 1979).
Chemical Laboratories
In 1957, a research worker in a laboratory synthesized 2,3,7,8-tetrabromo
dioxin. That same year, another researcher first synthesized 2,3,7,8-TCDD (about
20 grams) by chlorination of unsubstituted dioxin. In both cases, on completion of
these achievements, the researcher was hospitalized (Rappe 1978). The chemical
laboratory continues to be a potential source of human exposure to dioxins.
One case is reported involving three scientists in the United Kingdom (May
1973). Although it was believed that adequate precautions had been taken, all three
were afflicted with various disorders. Two of the scientists had been working on the
synthesis of dioxin standards. They had performed the synthesis under a fume
hood and had worn overalls and disposable plastic gloves. Both persons developed
chloracne in addition to other symptoms. The third scientist, who had been
working with dilute dioxin standards, had taken similar protective measures. He
did not develop chloracne but he exhibited other symptoms, including hirsutism
and excess cholesterol in the blood.
In 1978, Dow Chemical Company reported that an employee contracted
chloracne after disposing of laboratory wastes contaminated with dioxins. He
reportedly had not followed standard safety procedures. Dow has developed a set
of elaborate laboratory safety rules to be used when working with dioxins.
Similarly, stringent procedures are exercised by independent laboratories that
analyze samples containing dioxins. The Brehm Laboratory of Wright State
University, Dayton, Ohio, includes a specially equipped laboratory with restricted
access, specially trained personnel, and tight internal quality control based on
mandatory routine wipe tests. All personnel use disposable gowns, gloves, and shoe
covers. "Cradle-to-grave" control is exercised for all reagents, wash water,
disposable clothing, towels, and all other materials used or consumed in the
laboratory; nothing enters the sewer or is discarded as common trash. Everything
enters scalable transportation barrels to be discarded in an environmentally
acceptable manner. Gas chromatographs are vented through charcoal filter
cartridges, which are routinely discarded into the barrels. Any dusty samples are
handled in a special filtered glove box with total control of all dust and unused
sample material. This laboratory has experienced no incidents of dioxin poisoning
(Taylor 1980).
185
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Waste Handling
Another possible route of exposure to workers is the handling of production
wastes generated from manufacturing and formulation processes. Not only the
employees of the company that generates dioxin-containing wastes can be affected
by these wastes, but also those who work for contract waste disposal firms. The
incident at Verona, Missouri, indicates that the waste disposal company owner and
/or his employees did not recognize the dangers of wastes with potential dioxin
content.
The synthesis of pentachlorophenol and its use in wood treatment also generate
waste products. A current study sponsored by the EPA Office of Solid Wastes
includes an analysis of sludge samples from various locations within three
industrial plants that produce either trichlorophenol, pentachlorophenol, or
hexachlorophene (U.S. Environmental Protection Agency 1978d). Also being
sampled is a wood-preservation operation in which pentachlorophenol is used.
Initial results have shown low-ppm concentrations of hexa-CDD's, hepta-CDD's,
and OCDD in sludges resulting from PCP production. Concentrations of the di-
oxins are not specified, but it is stated that the levels are below those designated as
toxic in the published literature. Also, 0.06 ppm OCDD and low levels (not quanti-
fied) of hexa-CDD's and hepta-CDD's were found in the soil in the vicinity of the
product storage area.
186
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SECTION 6
HEALTH EFFECTS
INTRODUCTION
On a molecular basis 2,3,7,8-TCDD is perhaps the most poisonous synthetic
chemical. As shown in Table 35, only bacterial exotoxinsare more potent poisons.
Not only is this TCDD isomer extremely poisonous but it also has extremely high
potential for producing adverse effects under conditions of chronic exposure.
Human exposure to 2,3,7,8-TCDD has induced chloracne (an often disfiguring
and persistent dermatologic disorder), polyneuropathy (multiple lesions of
peripheral nerves), nystagmus (involuntary rapid movement of the eyeball), and
liver dysfunction as manifested by hepatomegaly (increase in liver size) and enzyme
elevations (Pocchiari, Silano, and Zampieri 1979). In animals, this compound has
been shown to be teratogenic, embryotoxic, carcinogenic, and cocarcinogenic
(Neubert and Dillman 1972; Courtney 1976; Kociba et al. 1978; and Kouri et al.
1978). It has been established that under certain conditions 2,3,7,8-TCDD can
enter the human body from a 2,4,5-T-treated food chain and can accumulate in the
fatty tissues and secretions, including milk (Galston 1979). The available data
indicate significant risks associated with the use of dioxin-contaminated
herbicides. Based upon the work of Van Miller et al., estimates done by accepted
risk assessment procedures indicate that daily human exposure to 0.01 /j. g (10 ng)
of 2,3,7,8-TCDD is the dosage expected to result in "incipient carcinogenicity."
Additionally, daily human exposure to 4 M g 2,3,7,8-TCDD would be expected to
result in a shortened lifespan, and daily exposure to 290 jug would likely result in
acute toxicity (Galston 1979).
Although 2,3,7,8-TCDD is considered to be the most toxic dioxin, others are
also cause for concern. Kende and Wade (1973) have established certain chemical
structural requirements that must be met for a dioxin to be toxic:
• Halogen substituents at positions 2, 3, and 7 are minimum structural
requirements.
• Bromine as a substituent is more active lexicologically than chlorine, which is
more active than fluorine.
• At least one hydrogen atom must remain on the dibenzo-/?-dioxin nucleus.
Another finding is that the ability for a dioxin to induce* various enzymes
correlates with its toxicity, as illustrated in Tables 36 and 37. As these tables show,
2,3,7,8-TBDD and Hexa-CDD are the only dibenzo-p-dioxin derivatives nearly
comparable to 2,3,7,8-TCDD in acute toxicity or ability to produce chloracne.
These two compounds are also comparable to 2,3,7,8-TCDD in induction of aryl
hydrocarbon hydroxylase (AHH). The compounds OCDD and 2,7-DCDD are
mildly toxic, with minimal ability to induce AHH. Thus bioassays of unknown
dioxin isomers based upon enzyme induction hold promise for predicting
biological activity and toxicity.
*An induced enzyme is one that is synthesized only in response to the presence of a certain substrate
or substrates.
187
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METABOLISM
In guinea pigs, 2,3,7,8-TCDD is moderately well absorbed from the
gastrointestinal tract and has a plasma half-life of about 1 month (Nolan et al.
1979). Although dibenzo-p-dioxin is rapidly converted by the microsome-N ADPH
system into polar metabolites, this system has little effect upon 2,3,7,8-TCDD
(Vinopal and Casida 1973). A large proportion of administered 2,3,7,8-TCDD
persists in unmetabolized form in the liver, partially concentrated in the
microsomal fraction in all species studied. This finding implies that the
unmetabolized compound, rather than a metabolite, is responsible for its toxic
effects in mammals. A recent study has shown that 2,3,7,8-TCDD is slowly
excreted via the biliary tract in the form of glucuronide and other more polar
metabolites (Ramsey 1979). The same study indicated that enterohepatic
recirculation of the compound was not extensive. Studies have indicated that its
toxicity is not mediated by:
• Inhibition of mitosis (cell division) in mammalian cells
• Alteration of glucocorticoid metabolism
• Alteration of thyroid hormone function
TABLE 35. TOXICITIES OF SELECTED POISONS3
Minimum lethal dose
Substance
Botulinum toxin A
Tetanus toxin
Diphtheria toxin
2,3,7,8-TCDDb
Saxitoxin
Tetrodotoxin
Bufotoxm0
Curare
Strychnine
Muscarmc
Diisopropylfluorophosphate
Sodium cyanide
Molecular weight
9.0 x 106
1.0 x 106
7.2 x 10*
322
372
319
757
696
334
210
184
49
(moles/kg)
3.3
1 0
4.2
3.1
2.4
2.5
5 2
7.2
1 5
52
1.6
2.0
X 10-15
x 1Q-'2
X 10-9
x 10'8
X 10-8
x 10-7
x 10-7
x 10-6
x 10"
x ID'5
x 10-4
a—Source Poland and Kende 1976 These data were compiled by Mosher et al, and the values
indicate only relative toxicity It should be noted that the values deal with different species,
routes of administration, survival times, and in one case the mean lethal dose rather than the
minimum lethal dose Except where noted, administration was by the intrapentoneal route in
mice
b—LD60 upon oral administration in the guinea pig
c—Intravenous injection in the cat
188
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TABLE 36. BIOLOGICAL PROPERTIES OF DIOXINS3
Compounds
2,3,7,8-TCDD
Unsubstituted dioxin
2,7-DCDD
2,3-DCDD
2,3,7-tn-CDD
2,3,7-tri-BDD
1,2,3,4-TCDD
1,3,6,8-TCDD
2,3,7,8-TBDD
Hexa-CDD (mixture)
OCDD
LD50(rat) Chloracne Teratogenic
(mg/kg) aptitude effect
0.04 +++ +++
>1000 o o
^2000 o ±
>1000 o o
>1000
>1000
>1000 o o
> 100 o o
< 1 +++
'v 100 + ++
^2000 o ±
Embryotoxic
effect
+++
0
±
o
0
o
++
+
a—Source Saint-Ruf 1978 Values for symbols were not reported
• Increasing serum levels of ammonia
• Inhibition of the synthesis of flavin enzymes or
• The effect of superoxide anion via DT-diaphorase stimulation (Beatty 1977).
Another aspect of 2,3,7,8-TCDD metabolism is its interaction with iron
metabolism. Rats given 1.7 /ig of the substance intragastrically have shown a 2-
fold increase in the serosal transfer of iron, whereas no effect was observed on the
mucosal iron uptake (Manis 1977). Sweeny (1979) has shown, however, that iron
deficiency protects mice from many of the toxic effects of 2,3,7,8-TCDD. In the
latter study, animals rendered iron-deficient were protected from elevated
porphyrin levels (including the consequent skin disease that resembles human
porphyria cutanea tarda) and liver damage. Since mixed function oxidase enzymes
were elevated in the iron-deficient mice, the authors speculated that depleted stores
of iron in tissue were responsible for the observed amelioration of toxicity. The
results of these studies have significant implications for toxicity in humans.
Persons with high dietary iron intake would be expected to be more susceptible to
2,3,7,8-TCDD toxicity than persons with marginal iron intakes. Similarly, females
might be less susceptible to its toxicity than males because they usually store less
iron in the body.
Pharmacokinetics and Tissue Distribution
Two studies have extensively examined the pharmacokinetics of 2,3,7,8-TCDD
(Piper, Rose, and Gehring 1973; Rose et al. 1976). Rose demonstrated that
elimination of this dioxin followed first-order kinetics, and he fit the data to the
189
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one-compartment open model. Table 38 shows the body burden of l4C-2,3,7,8-
TCDD in rats given a single oral dose of 1.0 ju g/ kg; the average fractional oral
absorption of 14C-2,3,7,8-TCDD was approximately 84 percent, and the
elimination half-life averaged 31 days. Piper's earlier study also found that after the
first 2 days following oral dosages of rats,elimination followed first-order kinetics.
-The results of this study, however, which are summarized in Figure 50, show that
only about 70 percent of ingested 2,3,7,8-TCDD was absorbed and the elimination
half-life was only about 17 days. Over a 21-day period, a total of 53 percent of the
ingested dose was excreted in the feces, while about 13 percent and 3 percent were
excreted in the urine and expired air, respectively.
Tissue distribution of ingested 2,3,7,8-TCDD has been examined in many
species, including rats, guinea pigs, and monkeys (Piper, Rose, and Gehring 1973;
Rose et al. 1976; Gasiewicz and Neal 1978; Van Miller, Marlar, and Allen 1976).
Rose et al. established that the accumulation of I4C-2,3,7,8-TCDD in rat liver
follows apparent first-order kinetics. In this study, the accumulation of 2,3,7,8-
TCDD in rat liver could be simulated by the following equation:
Ct=C,,(l-e-kt)
where C t = the concentration of I4C activity in the liver at time t
C ss = the concentration of I4C activity in the liver at steady state
K = elimination rate constant from the liver
TABLE 37. ENZYME INDUCTION3
Zoxazolamine
ALASb AHHC hydroxylase
Compounds (chick embryo) (chick embryo) (rat)
2,3,7,8-TCDD +++ 1.00 +++
Unsubstituted dioxm o
2,3-DCDD o 0.00
2,7-DCDD o 0.00
2,8-DCDD o 0.00
1,3-DCDD o 0.00
2,3,7-tn-CDD ++ 0.02
2,3,7-tn-BDD ++ 0.60
1,2,3,4-TCDD o 0.00
1,3,6,8-TCDD + 0.20
2,3,7,8-TBDD 1.00 +++
Hexa-CDD 0.80
OCDD 0.00 o
a—Source' Samt-Ruf 1978. Values for symbols not reported
b—Ammo-levulinic Acid Synthetase.
c—Aryl Hydrocarbon Hydroxylase
190
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TABLE 38. 14C BODY BURDEN ACTIVITY IN SIX RATS GIVEN A SINGLE
ORAL DOSE OF 1.0 jitg OF 14C-2,3,7,8-TCDD/kga
Sex
Male
Male
Male
Female
Female
Female
Mean ±SD
f
0.66
077
0.91
0.93
0.87
0.91
0.84 ±0.11
k (days-')
0.026 ±0.001b
0.018 ±0.001
0.021 ±0.000
0.022 ±0001
0.019 ±0.001
0.033 ±0.002
0.023 ±0.006
ty2 (days)
27
39
33
32
36
21
31 ±6
a—Source Rose et al 1976 Rose gives the following equation
Body burden = f (dose)e~kt
where f is the fraction of the dose absorbed, k, the elimination rate constant, t,/2, the body
burden half-life.
b—Confidence limits 95%
Values of Css equal to 0.25 jug equivalent 2,3,7,8-TCDD per gram of liver per
/ag dose, and k equal to 0.026 days-' were obtained by fitting experimental data.
In this study, the concentration of the dioxin in rat liver was 5 times greater than
that in fat, while concentrations in kidney, thymus, and spleen were I/ 12th to
I/50th of those in the liver. Rose et al. (1976) also assumed that first-order
elimination kinetics applied to accumulation of 2,3,7,8-TCDD in rat fat, and they
calculated values of Css andk equal to 0.058 ^g equivalent TCDD per gram of fat
per jug dose and 0.029 day1 , respectively. Additional clearance and
accumulation data were published by Fries and Marrow in 1975.
In a study of male guinea pigs, Gasiewicz and Neal (1978) found the highest levels
of radioactivity (percent of original dose per gram of tissue) on day 1 after injection
in the adipose tissue (2.36 percent), adrenals (1.36 percent), liver (1.13 percent),
spleen (0.70 percent), intestine (0.92 percent), and skin (0.48 percent). On day 15 of
this study, the level of l4C-2,3,7,8-TCDD in the liver had increased to 3.23
percent/g; increases were also noted in the adrenals, kidneys, and lungs, and
general decreases were seen only in adipose tissues and skin.
Van Miller et al. (1975) found that 40 percent of the radioactivity of an
administered dose of labeled 2,3,7,8-TCDD was concentrated in rat liver, whereas
less than 10 percent was concentrated in monkey livers. In this study, high
concentrations of the radioactivity were found in the skin, muscle, and fat of
monkeys. Thus, there appear to be significant differences in the tissue distribution
of 2,3,7,8-TCDD among various animal species.
One study examined the tissue distribution and excretion of labeled OCDD in
the rat (Norback 1975). A radioactive analog of OCDD at a daily dosage of about
12.4 mg/kg was administered for 21 days. Over 90 percent of the OCDD
administered was recovered in the feces as unabsorbed material. The major route of
elimination of absorbed OCDD in the rat was the urinary system, and the rate
corresponded to a biological half-life of about 3 weeks. After 21 days of
191
-------
administration, approximately 50 percent of the body burden of OCDD was found
in the liver; over 95 percent of the radioactivity in the liver was associated with the
microsomes and was equally distributed within the rough and smooth fractions.
The radioactivity in adipose tissue was about 25 percent of that in the liver.
Significant levels of radioactivity were also found in the kidneys, breast, testes,
skeletal muscle, skin, and serum.
25
20
TJ
0>
£ 15
u
o
Q
10
0)
CL
Each Point Represents
the Mean ± SE for
Three Rats
Figure 50. Excretion of 14C activity by rats following a single oral dose
of 50 M9/kg (0.14 MCi/kg) 2,3,7,8-TCDD.
Source1 Piper, Rose and Gehring 1973
192
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Enzyme Effects
Several investigations show that 2,3,7,8-TCDD has a dramatic influence upon
various enzyme systems in many species including man. The most notable were the
mixed-function oxygenases. For example, 2,3,7,8-TCDD is approximately 30,000
times more potent than 3-methylcholanthrene in inducing activity of the enzyme
aryl hydrocarbon hydroxylase (AHH) in rat liver (Poland and Glover 1974). This
dioxin is also a potent inducer of 6 -amino-levulinic acid synthetase in the liver of
chick embryo (Poland 1973). These properties of 2,3,7,8-TCDD have a
considerable influence upon its toxicity. For instance, its ability to act as a
cocarcinogen or to produce porphyria cutanea tarda depends upon alteration of
enzymatic systems. Before the effects on enzymatic systems are catalogued, an
examination of the mechanism of its effects on the cytochrome P-450-mediated
monooxygenase enzyme system may prove informative. This enzyme system
handles much of the influx of "foreign" chemicals and appears to rival the immune
system in complexity (Fox 1979).
A well-characterized subset of the P-450-mediated enzymes is a group of
cytochromes whose induction is regulated by one of a small number of genes. Fox
(1979) has termed this genetic system the Ah complex (for aromatic hydrocarbon
responsiveness). Work with 2,3,7,8-TCDD has demonstrated that the Ah locus
must involve a minimum of three gene products at each of two nonlinked loci, plus
a structural gene for cytochrome P] -450 (P-448) as well. Other investigators have
demonstrated that cytosolic binding sites for 2,3,7,8-TCDD enhance AH H activity
by de novo* protein synthesis of apocytochrome P-448, and that these binding sites
are not necessarily associated with AHH inducibility regulated by the Ah locus
(Guenthner and Nebert 1977; Kitchinand Woods 1978). It has been postulated that
the rate-limiting factor in AHH induction is protein synthesis of apocytochrome P-
448 (Kitchin and Woods 1978). Fox (1979) suggests that 2,3,7,8-TCDD may act in
a manner similar to steroid hormones. He postulates that the dioxin may ride its
receptor into a cell's nucleus, where it turns on specific Ah genes. Activation of
these genes would then lead to the requisite protein synthesis for AHH induction.
Figure 51 summarizes the mechanism of AHH induction proposed for 2,3,7,8-
TCDD and possibly the mechanism by which this substance produces other toxic
effects. As the figure shows, 2,3,7,8-TCDD moves into a cell and binds to a specific
cytosolic receptor. The receptor-dioxin complex then moves into a cell's nucleus,
where it "turns on" the synthesis of specific messenger RNAs, which direct the
synthesis of cytochrome Pr450. Other 2,3,7,8-TCDD molecules can then react
with newly formed cytochrome P,^t50, possibly to produce reactive intermediates.
These metabolites may be excreted as innocuous products, may afflict specific
critical target cells in other organs, or may act as carcinogens or cocarcinogens.
Several studies show that 2,3,7,8-TCDD induces many enzyme systems and
suppresses others. Studies with rats indicate that females are more susceptible than
males to enzyme alteration by the dioxin (Lucier et al. 1973). Further, 2,3,7,8-
TCDD induces the following enzymes in addition to AHH, 5-amino-levulinic
acid synthetase, and the cytochrome P-450-containing monooxygenases,
mentioned earlier:
• UDP glucuronyl transferase (Lucier 1975);
• Aldehyde dehydrogenase (Roper 1976);
• Glutathione transferase B (Kirsch 1975);
• DT-diaphorase (Beatty and Neal 1976);
• Benzopyrene hydroxylase (Lucier 1979);
'primary or of recent onset
193
-------
•
Reactive lntermediate_
mRNA's Direct Synthesis
of Specific Proteins
(Cytochrome P -450)
Reactive Intermediate
Binds Critical Target
Critical Target
in Other Cells
Drug Toxicity or
Initiation of Cancer
-------
• Glutathione S-transferase (Manis 1979);
• Ethoxycoumarin deethylase (Parkki and Aitio 1978).
Marselos et al. (1978) found that 2,3,7,8-TCDD decreases activity of the
following enzymes:
• UDP-glucuronic acid pyrophosphatase;
• D-glucuronolactone dehydrogenase;
• L-gluconate dehydrogenase.
The following enzymes have shown no effects upon exposure to 2,3,7,8-TCDD:
• NADPH cytochrome (Lucier et al. 1973);
• B-glucuronidase (Lucier et al. 1973);
• UDP-glucose dehydrogenase (Marselos et al. 1978);
• Epoxide hydrase (Parkki and Aitio 1978);
• Glycine N-acetyl transferase (Parkki and Aitio 1978).
As these lists indicate, the effects of 2,3,7,8-TC DD on more than a dozen enzyme
systems have been studied extensively.
Effects on Lipids
2,3,7,8-TCDD has dramatically altered the lipid profiles in laboratory animals
and man. One study examined the effects of both sublethal and lethal doses upon
the lipid metabolism of the Fischer rat (Albro 1978). A sublethal dose of 2,3,7,8-
TCDD caused a temporary increase in triglyceride and free fatty acid levels, with a
persistent decrease in levels of sterol esters. Lethal doses resulted in fatty livers and
large increases in serum cholesterol esters and free fatty acids, with little change in
triglyceride levels. These changes appeared to be due in part to damage sustained
by lysosomes. A decrease in acid lipase activity observed in the study also supports
the hypothesis that the 2,3,7,8-TCDD-induced myeloid bodies (see Figure 52) were
derived from damaged lysosomes and probably accounted for the increased levels
of cholesterol esters in animal livers. A mechanism by which 2,3,7,8-TCDD may
exert its toxic effects is suggested by the observed rapid, dose-dependent increase in
lipofuscin pigments.* Lipid peroxidation, which precedes the formation of
polymeric lipofuscins, is known to seriously damage membranous subcellular
organelles, including lysosomes.
Studies of workers occupationally exposed to 2,3,7,8-TCDD have shown lipid
abnormalities (Walker and Martin 1979; Poland et al. 1971). In Poland's study, 7 of
71 persons (10 percent) occupationally exposed to the dioxin in a plant
manufacturing 2,4-D and 2,4,5-T showed elevated serum cholesterol levels (greater
than 294 mg/100 ml). Walker's more recent study of eight dioxin-exposed workers
with chloracne showed significant abnormalities in lipid metabolism and liver
function. In this study, the levels of triglycerides and 7-glutamyl transpeptidase
(GGT)** were elevated in five men and were normal in the other three. In all of the
dioxin-exposed workers with chloracne, however, the levels of high-density
lipoprotein (HDL) cholesterol were below the method mean, total cholesterol
levels were above the method mean, and ratios of total to HDL cholesterol were
consistent with a higher-than-average risk of ischemic (oxygen insufficiency)
vascular disease. Two of the men in the study had experienced previous myocardial
infarction (heart attack), and one had experienced possible transient ischemic
'Bronze-colored (wear-and-tear) pigments.
**Liver enzyme.
195
-------
attacks (TIA's) (reversible cerebrovascular insufficiency). In any event, the lipid
abnormalities resulting from 2,3,7,8-TCDD exposure may be a significant risk
factor for ischemic vascular disease.
"**
Lipid
Droplet
Figure 52. Schematic of rat liver 13 days after administration of 2,3,7,8-TCDD
(50 M9/kg) Note concentric membrane array surrounding lipid droplet X20502.
Source Redrawn from Albro 1978
196
-------
GROSS AND HISTOPATHOLOGIES
The gross (macroscopic) and histopathologies (microscopic) of dioxin-exposed
chickens, rats, and monkeys have been examined extensively (Gupta et al. 1973;
Norback and Allen 1973; Allen 1967; Allen et al. 1975; Greig and Osborne 1978).
The chicken develops extreme morbidity and mortality at dietary concentrations of
2,3,7,8-TCDD that are only mildly toxic to rats, whereas response in the monkey is
intermediate (Norback and Allen 1973). At postmortem examination, the most
striking finding in dioxin-exposed animals is usually substantial loss of body fat.
Two types of lesions have been reported in all species studied: (1) involution of
the thymus; and (2) testicular alterations, including atrophy, necrosis, and
abnormal spermatocyte development. One lesion, hypertrophic gastritis, has been
observed only in primates. This lesion is characterized by marked hypertrophy of
the gastric (stomach) mucosa, which occurs in the fundic and pyloric regions
combined with small gastric ulcers penetrating the mucosa (Allen 1967).
In experiments with Macaco mulatto monkeys exposed to dioxins (Allen 1967;
Allen et al. 1975; Norback and Allen 1973), researchers found reduced
hematopoiesis (formation of blood cells) and spermatogenesis, degeneration of the
blood vessels, focal necrosis of the liver, and gastric ulcers. Under gross
observation, experimental monkeys exhibited obvious dilatation of the heart,
especially on the right side. Under microscopic examination, the cardiac muscle
fibers were distinctly separated by fluid, and individual muscle cells were
hypertrophic, with enlarged, distorted, and hyperchromic nuclei (see Figures 53
and 54). Although the lungs of the animals were not altered appreciably, isolated
areas of atelectasis (small areas of collapse), congestion, edema, and fibrosis were
observed. Livers from the monkeys were small, firm, and moderately yellow, with
many enlarged, multinucleated parenchymal cells. Necrosis of parenchymal liver
cells occurred in the centrilobular zone, and some areas of fibrosis occurred in the
periportal area. Spleens from the animals were small; the germinal centers were
surrounded by only scattered lymphocytes, and the blood sinuses were practically
devoid of cells. The seminiferous tubules of the testes had abundant spermatogonia
and sertoli cells; only a few primary spermatocytes were present, however, and no
spermatids or mature spermatozoa were observed. Gastrointestinal changes have
been described earlier.
Mesenteric (abdominal) lymph nodes of the monkeys were light tan and
edematous, microscopically resembling the splenic disarray of cellular
architecture. Grossly, the bone marrow resembled coagulated plasma.
Microscopically, only a few hematopoietic cells were seen in the marrow; these
were equally divided between members of the myeloid (white blood cell line) and
erythroid (red blood cell line) series. Changes in the skeletal muscle resembled
those of cardiac muscle. Skin from the experimental animals was dry and flaky;
loss of eyelashes with facial edema and petechiae (small hemorrhages) were
commonly observed. Microscopic changes in the skin are illustrated in Figure 55.
Along with facial edema, anasarca (widespread edema of abdomen and
extremities) was commonly observed.
The rat also has been studied extensively (Gupta et al. 1973; Norback and Allen
1973; Kociba et al. 1978; Greig and Osborne 1978). Gross pathological observation
indicated that rats died with jaundiced ears, subcutaneous tissues, and visceral
organs. Uterine size was decreased, and there was a generalized loss of
subcutaneous and abdominal fat. The liver and spleen were small, and the liver was
friable and dark tan. All thymuses were markedly atrophied, and hemorrhages
were present in the gastrointestinal tract and meninges.
Microscopic observation showed a relative depletion of lymphoid cells in the
spleen and lymph nodes, and markedly smaller thymic lobules with no
demarcation between the cortex and medulla. Rats given large doses of 2,3,7,8-
TCDD showed marked changes in liver cellular morphology and architecture, as
197
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illustrated in Figures 56 through 59. Hepatocytes were round and large, and the
hepatic cords were disorganized. Increased mitoses were seen in the liver
parenchyma (mass of cells), and some areas contained hepatocytes with seven to
ten nuclei (see Figure 56). Individual hepatocytes showed proliferation of smooth
endoplasmic reticulum and often distorted cell membranes. Also, the number of
lipid droplets are increased. Atretic (degenerative and distorted) changes were
Figure 53. Drawing of tissue from heart of monkey fed 2,3,7,8-TCDD; tissue
fixed with formalin and stained with hematoxyhn and eosin. Muscle cells
are hypertrophic with enlarged and distorted nuclei. X115.
Source: Redrawn from Norback and Allen 1973.
198
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noted in the ovarian follicles, and mucosol folds and glandular structures in the
uterus were atrophied. Epithelial cells of the renal tubules were foamy and
vacuolated with numerous hyaline droplets. Moderate to marked degenerative
changes were noted in the epithelial cells of the thyroid follicles, and there were
papillary projections into the lumen of the follicles. Focal hyperplasia (increased
cell number) was noted in the terminal bronchioles of the lung (Figure 60).
Congestion and elongation of the intestinal villi also were noted.
Mitochondrion
Myofibrils
!***
Figure 54. Drawing of heart tissue from monkey fed 2,3,7,8-TCDD. Myofibrils
of dilated cardiac fibers are separated, and the mitochondria are moderately
swollen. Tissue fixed with Veronal acetate-buffered osmium tetroxide solution
and stained with uranyl acetate. X9700.
Source: Redrawn from Norback and Allen 1973.
199
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Pathology of chickens exposed to dioxins is similar to that observed in other
animals (Norback and Allen 1973). Chickens succumbed very rapidly, with
hydropericardium (fluid in sac surrounding heart), hydrothorax (fluid in chest
cavity surrounding lungs), and ascites. They also developed liver necrosis,
hypoplastic testes, altered capillary permeability, and decreased hematopoiesis.
Gupta et al. (1973) report pathologic findings in guinea pigs and mice exposed to
2,3,7,8-TCDD. In guinea pigs, mitotic figures and loss of lipid vacuoles were
observed in the zona fasiculata, along with atrophy of the zona glomerulosa of the
adrenals. Guinea pigs also had widespread hemorrhages in the subserosal region of
the gastrointestinal tract, bladder, lymph nodes, and adrenals. Pathologic findings
observed in mice are similar to those noted in other animals.
Hair Follicle
Large
Keratin Cyst
Figure 55. Drawing of section of skin of monkey fed 2,3,7,8-TCDD Note the
presence of keratin cysts and the lack of a hair shaft in the hairfollicle.Tissuefixed
with formalin and stained with hematoxylin and eosin X15.
Source1 Redrawn from Norback and Allen 1973.
200
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ACUTE TOXICITY
The acute and subacute toxic potential of 2,3,7,8-TCDD in animals relative to
some other chlorodioxins and pesticides is illustrated in Tables 39 and 40. As the
tables indicate, 2,3,7,8-TCDD is a highly toxic material, several orders of
magnitude more potent than many pesticides. Some consider it to be the most toxic
small molecule made by man (Poland and Kende 1976).
Nuclei ~\>
Figure 56. Drawing of part of a multmucleated liver cell from a female rat
given 0 1 M9 of 2,3,7,8-TCDD/kg/day for 2 years. Uranyl acetate-lead citrate
stain. X1620
Source: Redrawn from Kociba, et al. 1978.
201
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Comparative Lethal Doses
Table 40 lists the LD50 values for various substituted dibenzo-p-dioxins. The
2,3,7,8-TCDD isomer is 3 to 100 times more potent than the other tetrachlorinated
isomers (Dow 1978). In comparison with 2,3,7,8-TCDD, the 1,3,6,8- and 1,3,7,9-
tetrachlorinated isomers have little biological activity (Rappe 1978). Both
octachlorodioxin and the unsubstituted dioxin are relatively nontoxic. Dioxin
Rough
Endoplasmic
Retjculum
Cell
Membrane
'^lw\
I \^
$• III')? (•«£,
r/.-V /i|| « >S" fPf r--HJ?*l.,p.d Droplet
«i\»,^^l.;A/J
'^v^J
^y "I&^.-K^W^ $
Smooth •%ji;i,
Endoplasmic
Reticulum
r
Lipid Droplet
Figure 57. Drawing of liver tissue from rat fed 2,3,7,8-TCDD. Tissue sample fixed
in Veronal acetate-buffered osmium tetroxide solution and stained
with uranyl acetate. X20400
Source: Redrawn from Norback and Allen 1973.
202
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structure-activity relationships are discussed in a later subsection. The LD^ values
for 2,3,7,8-TCDD in rats, guinea pigs, and rabbits are presented in Table 41. The
male guinea pig appears to be the most sensitive, having an LD50 of 0.0006 mg/kg
(0.6 /^g/kg). The LD50 values in monkeys exposed to a single oral dose range
from 50 to 70 jug/kg body weight (McConnell, Moore, and Dalgard 1978). In
mice, the LD50 is 0.2837 rag/kg body weight (McConnell et al. 1978).
Normal
Membranes
Figure 58. Drawing of normal membrane junctions from the periportal region
of a test animal 42 days after administration of 200 fjg/kg 2,3,7,8-TCDD.
Uranyl acetate and lead citrate stain X16000.
Source: Redrawn from Greig and Osborne 1978.
203
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Target organs for the acute toxic effects of TCDD in commonly studied
laboratory animals are listed in Table 42. All species of animals studied by Moore
et al. (1976) showed severe thymus involution and testicular degeneration.
Reduction in the white pulp of the spleen combined with bone-marrow hypoplasia
(decreased cell number) were other common effects. Mice exhibited the greatest
degree of liver toxicity, and female monkeys showed the most skin lesions and bile-
Figure 59. Drawing of distorted periportal membrane junction, showing loss
of continuity of plasma membranes between parenchymal cells (42 days after
200 fig/kg 2,3,7,8-TCDD); small blebs of normal membrane remain
Uranyl acetate and lead citrate stain. X42500
Source: Redrawn from Greig and Osborne 1978.
204
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duct hyperplasia. Ascites was common in monkeys, but was more prominent in
mice. Hyperplasia of the renal pelvis and urinary bladder was common in guinea
pigs. Gastrointestinal hemorrhages were common in both mice and guinea pigs.
Aquatic Toxicity
No data are available concerning the acute toxicity of 2,3,7,8-TCDD on
saltwater organisms, and there are only scant data relative to freshwateraquatic life
Figure 60. Focal alveolar hyperplasia near terminal bronchiole within lung of rat
given 2,3,7,8-TCDD at dosage of 0.1 M9/kg per day. H & E Stain. X100.
Source: Redrawn from Kociba et al 1978.
205
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(U.S. EPA 1978c). Exposures of fish and invertebrate species to the dioxin in water
and food and by intraperitoneal injection have demonstrated a variety of adverse
effects at very low concentrations. Model ecosystem studies have demonstrated
bioconcentration factors for 2,3,7,8-TCDD of 3,600 and 26,000 over a period of 3
to 31 days (Isensee and Jones 1975). Exposure of coho salmon to an aqueous
concentration of 0.000056 pig/liter under static conditions for 96 hours resulted
in 12 percent mortality, whereas mortality of control fish was 2 percent (Miller,
Norris, and Hawks 1973). In the same study, all coho salmon exposed to 0.056
fig/liter for 24 hours were dead within 40 days. Isensee (1978) reports that 3 ppt
of 2,3,7,8-TCDD is acutely toxic to mosquito fish.
Structure-Activity Relationships
The general structure-activity relationships of dibenzo-p-dioxins are presented
earlier in this section. Briefly, at least one hydrogen atom and a minimum of three
laterally placed halogen atoms must be present in the dioxin structure for it to be
toxic (Kende and Wade 1973).
TABLE 39. TOXICITIES OF ORGANIC PESTICIDES AND 2,3,7,8-TCDD3
Maximum dose producing no
observed adverse effect
Compound (mg/kg per day)
2,3,7,8-TCDD
Disolfoton and phorate
Diazinon
Parathion and methyl parathion
Aldicarb
Malathion
Silvex(2,4,5-TP)
Hexachlorobenzene
Hexachlorophene
Toxaphene
MPCA
Pentachlorophenol
Butachlor
Methoxychlor
2,4,5-T
Bromacil
2,4-D
Ortho- and paradichlorobenzene
Atrazine
Captan
Arachlor
Methyl methacralate
Di-/?-butyl phthalate
Styrene
10'5
0.01
0.02
0.043
0.1
0.2
0.75
1.0
1.0
1.25
1.25
30
100
10.0
10.0
12.5
12.5
13.4
21.5
500
100.0
1000
110.0
133.0
a—Source. National Academy of Science 1977
206
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TABLE 40. ACUTE TOXICITIES OF DIOXINS3
Substitutions with chlorine
None0
2,8
2,3,7
2,3,7,8
1,2,3,7,8
1,2,4,7,8
1,2,3,4,7,8
1,2,3,6,7,8
1,2,3,7,8,9
1,2,3,4,6,7,8
1,2,3,4,6,7,8,9°
1-NO2-3,7,8
1-NH2-3,7,8
1-NO2-2,3,7,8
1-NH2-2, 3,7,8
LD60(
Guinea pigs
>300,000.0
29,444.0
0.6-2.0
3.1
1,125.0
72.5
70-100
60-100
>600;7180d
>30,000.0
>30,000.0
47.5
194.2
Mg/kg)b
Mice
>50 x !03(i.p.)e
>3,000.0
283.7
3375
>5,000.0
8250
1,250.0
>1 ,440.0
>4 x 106
>2,000.0
>4,800.0
a—Unless otherwise noted, taken from McConnell et al. 1978.
b—All values are for oral doses unless noted; test period is 30 days
c—World Health Organization, IARC Monographs on the Evaluation of the Carcinogenic Risk
of Chemicals to Man 15 69-70, August 1977
d—EPA-RPAR on Pentachlorophenol Federal Register 43(202).48454, October 18, 1978
e—Interpentoneal
TABLE 41. ACUTE TOXICITIES OF 2,3,7,8-TCDD
FOR VARIOUS SPECIES8
Species
Sex
Route of exposure
Dosage
(LD50 mg/kg)
Rat
Guinea pig
Rabbit
Male
Female
Male
Male
Female and male
Female and male
Female and male
Oral
Oral
Oral
Oral
Oral
Dermal
Interperitoneal
0.0220
00450
0.0006
0.0021
0.1150
0.2720
XI.2520
a—Source Schwetz et al 1973
207
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TABLE 42. SUMMARY OF ACUTE TOXICITY EFFECTS
OF 2,3,7,8-TCDDa
Monkeys
Mice Guinea pigs (female)
Thymus involution +++ +++ +++
Spleen reduction (white pulp) + + +
Bone-marrow hypoplasia ± ++ +
Liver, megalocytosis/degeneration +++
Bile-duct hyperplasia ± ± +++
Testicular degeneration ++ +++ N/A
Renal-pelvis hyperplasia ++ +
Urinary-bladder hyperplasia ++
Adrenal-cortical atrophy ++
(Zona Glomerulus)
Hemmorhage: Intestinal + +
Adrenal ++
Ascites ++ +
Cutaneous lesions - - +++
a—Source Moore et al. 1976 Key as follows - no effects
+ mildly affected
++ moderately affected
+++ severely affected
Studies have shown that a dioxin's ability for enzymatic induction correlates well
with its toxic potential and thus its structure. In one study, age- and sex-related
differences in hepatic mixed-function oxidase activity in rats apparently were
inversely correlated with the 20-day LD50 of 2,3,7,8-TCDD (Beatty et al. 1978).
The study also examined the effects of administering inducers and inhibitors of the
hepatic mixed-function oxidase enzyme systems of the 20-day LD50 of 2,3,7,8-
TCDD in rats. In all cases, there was an inverse relationship.
CHRONIC TOXICITY
Although chloracne is a common indicator of 2,3,7,8-TCDD exposure in
humans and some animals, chronic exposure to this dioxin can affect many organ
systems. In addition to chloracne, another dermatologic manifestation of exposure
is porphyria cutanea tarda (PCT), a photosensitive dermatosis caused by altered
porphyrin metabolism. Hepatic (liver) toxicity resulting from prolonged exposure
to 2,3,7,8-TCDD is common in animal models and has been observed in human
workers after industrial exposures. In animal models, the dioxin has caused
damage to renal (kidney) tubular epithelium and caused alteration in levels of
serum gonadotropin (pituitary hormones influencing reproductive organs). A
208
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profound deficit in cell-mediated immunity is produced in experimental animals
exposed to 2,3,7,8-TCDD in the perinatal period. Along with thymic atrophy,
exposure to 2,3,7,8-TCDD leads to a depletion of cells in the spleen, lymph nodes,
and bone marrow. Hypertrophic gastritis has been observed frequently in exposed
monkeys. Alterations in lipid metabolism produced by 2,3,7,8-TCDD exposure
may greatly increase the risk of atherogenesis in occupationally exposed workers.
Neuropsychiatric symptoms including neurasthenia (depressive syndrome with
vegetative symptoms) and peripheral neuropathies have been attributed to 2,3,7,8-
TCDD exposure. These various aspects of chronic toxicity are discussed in the
following subsections.
Dermatologic Effects
Dermatologic diseases are perhaps the most sensitive indicators of 2,3,7,8-
TCDD exposure and toxicity in humans. Although chloracne is the most
frequently observed dermatosis, PCT has been observed in as many as 10 percent of
a group of occupationally exposed workers (Purkyne et al. 1974).
Chloracne—
Chloracne, which is characterized by comedones, keratin cysts, pustules,
papules, and abscesses, is a classical sign of 2,3,7,8-TCDD exposure in humans
(U.S. NIEHS IARC 1978). Chloracne can be caused by ingestion, inhalation, or
skin contact with chlorodibenzodioxins, and the disease may clear in a few months
or persist for as long as 15 years (Crow 1978). All chlorodibenzodioxins that are
acnegenic are also systemic toxins, but the external dose needed to produce
chloracne is far lower than that needed to cause systemic toxicity (Crow 1978).
Chloracne, which can be an extremely refractory form of occupational acne, was
first described by Von Bettman in 1897 (Taylor 1974). The symptoms may appear
weeks or months after the initial exposure to chlorodibenzodioxins. Rabbits can be
used to test the acnegenicity of a chlorodibenzodioxin, because these compounds
induce acneform lesions when applied to the skin of rabbit ears (Kimmig and
Schulz 1957).
Kimmig and Schulz (1957) provided a detailed description of the clinical
manifestations of chloracne that developed in 31 workers in a German plant
producing 2,4,5-T in 1954. In heavily exposed workers, dermatitis of the face
accompanied by erythma and swelling was first observed. As these symptoms
faded, acneform lesions appeared on the face and later on other parts of the body.
In most workers, the initial manifestations of chloracne were patches of open
comedones (blackheads) followed by pustules in the zygomatic region (cheeks) of
the face. Upon initial examination, the observed skin changes included many
blackheads, pinhead- to pea-sized closed comedones (whiteheads), associated
follicular hyperkeratosis, inflamed pimples, pustules, and large boils. The face,
ears, throat, and neck were affected in all cases; in severe cases, lesions were
encountered on the breast, back, epigastrium (skin of upper abdomen), genitals,
and extensor surfaces of the arms and thighs.
Porphyria Cutanea Tarda (PCT)—
Porphyria cutanea tarda (PCT) is a skin condition that usually occurs as a
photosensitive dermatosis and is characterized by development of vesiculobullous
(blistering) lesions over exposed areas (Benedetto and Taylor 1978). The
dermatosis is precipitated by minor trauma, and may result in areas of healed
bullae, crusts, scars, and milia. Hyperpigmentation, hypertrichosis (excessive
growth of hair), and schlerodermoid (tightening of skin over the fingers) changes
can also occur, along with dark red urine (Benedetto and Taylor 1978). Animal
studies have shown that 2,3,7,8-TCDD is the porphyrinogenic compound formed
during the manufacture of 2,4,5-T. Jones and Sweeney (1977) have shown that
uroporphyrinogen decarboxylase (UD) levels can be depressed in rats given
209
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2,3,7,8-TCDD. Their results indicate that the dioxin depresses UD levels
sufficiently to produce the biochemical disturbance of PCT. Sweeney (1979) notes
that iron-deficient mice are protected from porphyria produced by 2,3,7,8-TCDD
exposure.
Hepatic Effects
The hepatotoxicity of 2,3,7,8-TCDD appears to be dose-dependent, and the
severity of any changes produced varies among species (Gupta 1973). In rats and
rabbits, hepatic necrosis produced by this compound is probably a contributing
cause of death, whereas hepatic necrosis and liver insufficiency are less extensive in
mice and are minimal relative to these disorders observed in guinea pigs and
monkeys (U.S. NIEHS IARC 1978). Van Miller et al. (1977) noted liver necrosis
and bile duct hyperplasia in a group of rats fed 1.0, 0.6, and 0.05 ppm 2,3,7,8-
TCDD for 65 weeks. In a 13-week toxicity study in which the dioxin was
administered orally to rats, doses of 1.0 jug/kg per day increased the levels of
serum bilirubin and alkaline phosphatase and caused pathologic changes in the
liver; doses of 0.1 Mg/kg per day caused a slight degree of liver degeneration
(Kociba et al. 1976). The histopathologic changes in rat liver resulting from 2,3,7,8-
TCDD exposure were described earlier.
Renal Effects
Several recent studies have examined the effects of 2,3,7,8-TCDD upon renal
function in the rat (Anaizi et al. 1978; Hook et al. 1978). Anaizi et al. studied the
steady-state secretion rate of phenosulfonphthalein (PSP) in rats pretreated with
10 pig/ kg of 2,3,7,8-TCDD 5 to 7 days prior to in vivo measurements. The results
were as follows:
• A significant increase in the tubular secretion rate of PSP occurred at low
plasma levels of PCP.
• There was no increase in the maximum secretory capacity for PSP (Tm-
PSP).
• A significant change in the glomerular filtration rate from 1.17 to 0.90
ml/ min per gram of wet kidney weight was observed in treated rats without a
change in the mean arterial pressure.
Anaizi et al. inferred from this study that glomerular structures in rats are highly
sensitive to 2,3,7,8-TCDD.
Hook et al. (1978) examined renal accumulation of p-aminohippurate (PAH)
and jV-methyl-nicotinamide (NMN) in rats given 10, 25, or 50 Mg/kg 2,3,7,8-
TCDD. In the 10 /ug/kg dose group, only NMN accumulation was slightly
decreased at 7 days. At 25 jug/ kg, the capacity of renal tissue to transport both
PAH and NMN was reduced 7 days after exposure. The GFR and effective renal
plasma flow were decreased in rats after doses of 25 or 50 jug/kg. Volume
expansion did not alter this relationship in the study. Thus these two independent
studies confirmed the ability of 2,3,7,8-TCDD to decrease renal function in the rat.
Endocrine Effects
It has been known for some time that 2,3,7,8-TCDD exposure in man is
associated with hormonal imbalances that lead to acne, hirsutism, and loss of
libido. Recently it has been shown that 2,3,7,8-TCDD can also have a dramatic
effect upon hormones involved in reproduction. A recent study has indicated a
suppressive effect upon testicular microsomal cytochrome P-450 content in guinea
pigs (Piper 1979). Another study has shown that 2,3,7,8-TCDD increases serum
thyroid stimulating hormone in humans 4- to 5-fold, and preliminary observations
210
-------
indicate that serum levels of prolactin and follicle stimulating hormone are affected
in rats following treatment with the dioxin (Gustafsson and Ingelman-Sundberg
1979). Testosterone hydroxylation in the 2 /3-and 16 a-positions has been reduced
by 50 percent in rats receiving less than 1 jug/ kg of 2,3,7,8-TCDD orally (Hook et
al. 1975). Similarly, exposures of female rats have shown 3- to 5-fold increases in
the following enzyme activities (Gustafsson and Ingelman-Sundberg 1979):
1. la- and 6 /3 -hydro xylases active on 4-androstene-3,17-dione;
2. 7«- and 2 )3-hydroxylases active on 5 a-androstane-3a , 17 0-diol; and
3. 16 a- and 6 /3-hydroxylases active on 4-pregnene-3,10-dione.
One recent study examined hormonal alterations in female rhesus monkeys fed a
diet containing 500 ppt of 2,3,7,8-TCDD per day for 9 months (Barsotti,
Abrahamson, and Allen 1979). Steroid analysis at 6 months showed alterations in
five of seven animals treated. Progesterone levels in three animals decreased to 72.4
percent, 51.9 percent, and 47.3 percent of their pretreatment values. During the
same interval, estradiol levels in two of these animals also decreased to 50.4 percent
and 43.2 percent of the control values. The remaining two animals with
abnormalities showed anovulatory patterns for both steroids. Estradiol never rose
above 30 pg/ ml of serum and progesterone remained below 400 pg/ ml of serum
throughout the menstrual cycles. After these analyses, all animals were bred. All of
the control animals conceived and gave birth to healthy infants. The two dioxin-
treated animals in which estradiol and progesterone levels had remained normal
did conceive, but one animal aborted the conceptus. Several other treated monkeys
conceived, but all subsequently aborted. The one dioxin-treated animal that
carried a fetus to term delivered a normal, healthy infant. After nine months, the
only monkey that had showed hormonal alterations and survived was placed back
on the control diet and subsequently delivered a normal, healthy infant.
Immunologic Effects
Exposure to 2,3,7,8-TCDD has caused thymus atrophy in all mammalian species
studied. As illustrated in Table 43, impairment of cellular immunity has been a
constant finding in studies of the effects of this dioxin on the immune system of
animals. Thymus (T-)-dependent lymphocytes are most affected by the exposure;
however, T-helper-cells are less compromised than other types of T-cells (Faith and
Luster 1977).
Suppression of cell-mediated immunity appears to be age-related in the mouse
and rat; perinatal exposure causes the greatest effect (Luster et al. 1978). It is
important to recognize that TCDD can produce immunosuppressive effects at
exposure levels too low to produce clinical or pathological changes (Thigpen et al.
1975).
Many studies have examined the effects of exposure to 2,3,7,8-TCDD on
impairment of cell-mediated immunity. Several studies have examined the effects
of either postnatal or both pre- and postnatal exposure of rat pups by maternal
dosing (Faith and Luster 1977; Luster et^al. 1978). Results indicated that cell-
mediated immune functions were depressed up to 133 days of age in both groups
but less severely in animals exposed only postnatally. In addition, the ratio of
thymus to body weight was depressed up to 145 days of age in prenatally exposed
rats, but the ratio was suppressed only up to 39 days of age in the postnatally
exposed group. These studies established that depression of T-cell function is
selective in that helper T-cell function was spared. Vos and Moore (1974)
demonstrated that cell-mediated immunity in 1-month old rats was depressed only
when toxic doses of 2,3,7,8-TCDD were administered. In vitro testing has
demonstrated that DNA, RNA, and protein synthesis in splenic lymphocytes is
severely inhibited when mouse spleens are only briefly exposed to 10~7 millimolar
solutions of 2,3,7,8-TCDD (Luster 1979a).
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TABLE 43. EFFECTS OF IN VIVO 2,3,7,8-TCDD EXPOSURE
ON FUNCTIONAL IMMUNOLOGICAL PARAMETERS3
Species Parameter
Effect" Reference
Guinea pig Delayed type hypersensitivity
Rat Delayed type hypersensitivity
Rat Graft versus host activity
Mouse Graft versus host activity
Rat, mouse Rejection of skin allografts
Rat Lymphocyte transformation by PHA and Con A
Mouse Lymphocyte transformation by PHA
Guinea pig Antibody response to tetanus toxoid
Rat Antibody response to bovine y-globulm
+° Vos et al. 1 973
+d/-c Moore and Faith 1976; Vos et al. 1973
+d Vos and Moore 1974
+c/-e Vos and Moore 1974; Vos et al. 1973
+d Vos and Moore 1974
++d Vos and Moore 1974; Moore and Faith 1976
+°/-e Vos and Moore 1974
_c,f/+c,8 Vos etal. 1973
_
-------
Multiple studies have examined the effects of 2,3,7,8-TCDD exposure upon in
vivo susceptibility to pathogenic organisms. Thigpen et al. (1975) administered
sublethal levels of the dioxin to mice and then subjected them to challenges with
Salmonella hern and Herpesvirus suis. At dose schedules of 1 jug/kg weeklyfor4
weeks, salmonella infection led to significant increases in mortality and reduction
of time from infection to death. The dioxin exposure had no apparent effect upon
the outcome of infection with Herpesvirus suis. Other researchers found that
mouse pups from mothers fed up to 5 ppb of 2,3,7,8-TCDD withstood a live
Listeria challenge as well as did the controls; however, maternal feeding at 2,3,7,8-
TCDD levels as low as 1 ppb rendered offspring more sensitive to challenge with
endotoxin (cell walls of gram negative bacteria) (Thomas and Hinsdill 1979).
Nonspecific killing and phagocytosis* of Listeria monocytogenes in mice were not
influenced by administration of 2,3,7,8-TCDD (Vos et al. 1978). In the same study,
treatment with the dioxin did not affect macrophage reduction of nitro-blue-
tetrazolium, and the authors speculated that endotoxin sensitivity in treated
animals is not the result of altered phagocytic function of macrophages. Similarly,
challenge with pathogenic streptococcus in aerosol form led to similar mortality
rates among treated mice and controls (Campbell 1979).
Humoral immunity and B-lymphocyte function are resistant to the toxic effects
of 2,3,7,8-TCDD. Faith and Luster (1977) found that humoral immune responses
to bovine gamma globulin were not suppressed in rats treated with the dioxin.
Luster (1979b) then demonstrated that T-lymphocytes are much more susceptible
to dioxin-induced immuno-suppression than B-lymphocytes with mitogens
specific for lymphocyte subpopulations. By measuring the antibody response
against tetanus toxoid in guinea pigs, Vos et al. (1973) showed only a slight decrease
in humoral immunity in 2,3,7,8-TCDD-treated animals. Thomas and Hindsill
(1979) demonstrated normal primary and secondary antibody responses in treated
mice.
Hematologic Effects
One of the major target organs for TCDD toxicity is the hematopoietic system.
Although many species have been studied, anemia has been observed only in rhesus
monkeys (Allen 1967). This anemia was of an aplastic type (characterized by lack of
cells in bone marrow) and was accompanied by atrophic bone marrow. The only
abnormalities of the hematopoietic system noted in 2,3,7,8-TCDD-treated rats
have been thrombocytopenia (increased numbers of platelets) and terminal
elevated packed red cell volumes secondary to hemoconcentration (Weissbergand
Zinkl 1973). In this study, the platelet counts of treated rats were significantly
reduced and their bone marrows contained normal numbers of megakaryocytes.
Zinkl et al. (1973) studied the hematologic effects of exposing guinea pigs and mice
to TCDD. The leukocyte and lymphocyte counts in mice given a single oral dose of
as little as 1.0 jug/kg TCDD were significantly lower after 1 week. A similar
relationship was observed in guinea pigs treated with tetanus toxoid or
Mycobacterium tuberculosis. In mice, the lymphopenia (decreased numbers of
lymphocytes) was reversed 5 weeks after exposure to the dioxin.
Gastrointestinal Effects
Two studies have explored the effect of dibenzo-p-dioxins upon intestinal
absorption of nutrients. Ball and Chhabra (1977) used in vitro everted sac and in
situ closed loop techniques to study the effect of a toxic dose of 2,3,7,8-TCDD (100
H g/ kg po) on adult male rats. Glucose uptake declined during the first few hours
following dosage, rose above controls between one and two weeks, and declined
*The process by which cells engulf and destroy foreign material.
213
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again after three weeks. Leucine uptake was depressed throughout the study.
Madge (1977) studied the effects of 2,3,7,8-TCDD and OCDD on function of the
small intestine in mice. He found that absorption of D-glucose decreased following
a single oral dose of each of the compounds. No effect was noted on the absorption
of D-galactose, L-arginine, or L-histidine. Total fluid transfer was generally
unaffected by treatment with either compound, and D-mannose, an exogenous
energy source, abolished the apparent malabsorptive effects of D-glucose in treated
animals.
Neuropsychiatric Effects
Two studies have examined the neuropsychological function of rats exposed to
2,3,7,8-TCDD. Creso et al. (1978) found that exposure induced irritability,
aggressiveness, and restlessness in rats, without acquisition or loss of a conditioned
avoidance reflex. In this study, the dioxin stimulated the activity of adenyl cyclase
in the rat brain striatum and hypothalmus in vitro. It also enhanced the stimulatory
effect of dopamine on striatal adenyl cyclase; however, this action was blocked by
haloperidol. The study also showed that 2,3,7,8-TCDD acted synergistically with
histamine in stimulating the hypothalmic adenyl cyclase.
Elovaara et al. (1977) showed that treatment with 2,3,7,8-TCDD caused: 1) an
increase in acid proteinase activity in the brains of normal Wistar rats, 2) reduction
of RNA and protein contents in heterozygous Gunn rats, and 3) no changes in
homozygous Gunn rats.
Purkyne et al. (1974) found various psychiatric and neurological complaints in a
cohort of 55 workers occupationally exposed to 2,3,7,8-TCDD. Seventeen subjects
showed neurological abnormalities. The most common disorder was
polyneuropathy of the lower extremities (confirmed by electromyography). Most
of these patients suffered from psychiatric disorders such as severe neurasthenia
syndromes with vegetative symptoms. These workers complained of weakness and
pain in the lower extremities, somnolence, insomnia, excessive perspiration,
headache, and various sexual disorders.
DEVELOPMENTAL EFFECTS
A brief review of the pertinent nomenclature is given here to characterize the
several developmental effects discussed in this section. The terms embryotoxicity
and fetotoxicity denote all transient or permanent toxic effects induced in an
embryo or fetus, regardless of the mechaniam of action. These are the most
comprehensive terms. A special fetotoxic effect is teratogenicity, which is defined
as an abnormality originating from impairment of an event that is typical in
embryonic or fetal development. For example, fetal growth retardation is a
fetotoxic but not a teratogenic effect of 2,3,7,8-TCDD (Neubert et al. 1973).
The first clue to the teratogenic and fetotoxic potential of 2,3,7,8-TCDD resulted
from a National Cancer Institute study begun in 1964 to evaluate the carcinogenic
and teratogenic potential of a number of herbicides (Collins and Williams 1971). In
this study, 2,4,5-T and 2,4-D were shown to induce increased proportions of
abnormal fetuses in hamsters. Courtney (1970) demonstrated the teratogenicity of
2,4,5-T containing approximately 30 ppm of 2,3,7,8-TCDD in two strains of mice.
Subsequent investigations studied the fetotoxicity and teratogenicity of both 2,4,5-
T and 2,3,7,8-TCDD in a number of species.
Teratogenicity
Courtney (1970) showed that 2,4,5-T containing 2,3,7,8-TCDD increased the
incidence of cleft palate in both C57BC/6 and AKR mice. Neubert et al. (1972),
using the purest available sample of 2,4,5-T, showed that at doses higher than 20
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mg/kg given orally during days 6 to 15 of gestation, the frequency of cleft palate
was significantly increased in NMRI mice. The maximal teratogenic effect was
produced when the drug was administered on days 12 or 13 of gestation. In the
same study, doses exceeding 1 /^g/kg of 2,3,7,8-TCDD produced an increased
rate of cleft palate; maximal teratogenicity occurred with administration on days 8
and 11 of gestation. Although Courtney and Moore (1971) found no potentiation
of teratogenicity with combinations of 2,4,5-T and 2,3,7,8-TCDD, Neubert and co-
workers found that 1.5 ppm of 2,3,7,8-TCDD administered with 30 to 60 mg/kg
2,4,5-T potentiated the increase in cleft palate frequency. Moore and co-workers
(1973) found that the mean average incidence of cleft palate was 55.4 percent in
mice exposed to 3 ;ug/kg 2,3,7,8-TCDDondays lOto 13 of gestation. In 1976, the
threshold teratogenic dose of 2,3,7,8-TCDD in CF-1 mice was estimated to be 0.1
jug/kg per day (Smith, Schwetz, and Nitchke 1976). In golden hamsters, oral
administration of 2,4,5-T containing dioxin on days 6 to 10 of gestation increased
the incidence of absence of the eyelid (Collins and Williams 1971). Although
2,3,7,8-TCDD is fetotoxic in primates at doses as low as 50 ppt, it has not been
shown to be teratogenic in this species (Schantz et al. 1979).
Fetotoxicity and Embryotoxicity
In general, 2,4,5-T and 2,3,7,8-TCDD produce fetotoxicity at doses that do not
produce teratogenic effects in a wide variety of species. Fetotoxic effects of 2,4,5-T
containing 2,3,7,8-TCDD were first noted in Courtney's original work (1970). Both
species of mice studied showed increased incidences of cystic kidneys, while in rats,
fetal gastrointestinal hemorrhages and increased ratios of liver to body weight were
also noted. Highman and Schumacher (1977) later demonstrated that cystic
kidneys in mice exposed to 2,4,5-T containing 2,3,7,8-TCDD were due to
retardation in fetal renal development and downgrowth of the renal papilla into the
pelvis. The results of this study demonstrated a retarded development of fetal renal
alkaline phosphatase, and thus support the hypothesis that cystic kidneys in mice
are a fetotoxic and not truly a teratogenic effect. Moore et al. (1973) proved that
prenatal and postnatal kidney anomalies had a common etiology, and the
incidence and degree of hydronephrosis* was a function of dose and of the length of
exposure of a target organ. Other fetotoxic effects of 2,4,5-T and 2,3,7,8-TCDD
include thymic atrophy, fatty infiltration of the liver, general edema, delayed head
ossification, low birthweight, fetal resorptions, and embryolethality.
Many studies have examined the fetotoxic effects of 2,4,5-T and 2,3,7,8-TCDD
on various species. In a study of the effects of 2,3,7,8-TCDD on the rat, no adverse
effects were noted at the 0.03 yug/kg level; but fetal mortality, early and late
resorptions, and fetal intestinal hemorrhage were observed in groups given 0.125 to
2.0 yug/kg,. the incidence increasing as the dose increased (Sparschu, Dunn, and
Rowe 1971). In the CD rat, 2,4,5-T was neither teratogenic nor fetotoxic;
however, 2,3,7,8-TCDD produced kidney anomalies (Courtney and Moore 1971).
In golden hamsters, 2,4,5-T containing 2,3,7,8-TCDD caused delayed head
ossification in a dose-dependent fashion (Collins and Williams 1971). Cystic
kidneys occurred unilaterally in 58.9 percent and bilaterally in 36.3 percent of mice
pups exposed to 1 fig/kg 2,3,7,8-TCDD (Moore et al. 1973). Murray (1978)
reports a three-generation study of rats exposed to 0.001, 0.01, or 0.1 ;ug/kg of
2,3,7,8-TCDD. Through three successive generations the reproductive capacity of
rats ingesting the dioxin was clearly affected at dose levels of 0.01 and 0.1 jug/kg
per day, but not at 0.001 Mg/kg per day.
In the most recent primate study, eight adult female rhesus monkeys were fed a
diet containing 50 ppt 2,3,7,8-TCDD for 20 months (Schantz et al. 1979). After 7
months attempts were made to breed the females. In this group there were four
*Dilation of renal pelvis usually associated with an obstructed ureter
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abortions and one stillbirth. All eight control animals reproduced successfully. In
the dioxin-exposed group, two animals were not able to conceive and two were able
to carry their infants to term.
One study examined the fetotoxic potentials in mice of other members of the
dibenzo-p-dioxin class of compounds (Courtney 1976). None of the dibenzo-p-
dioxins studied were as toxic as 2,3,7,8-TCDD, and some of the compounds could
be considered relatively nontoxic. Although the mixture of di-CDD and tri-CDD
produced a slight increase in the number of abnormal fetuses, it is doubtful that the
malformations were produced by the mixture. Most of the malformations (a mild
form of hydronephrosis) were in mouse pups from one litter, and no malformations
were observed at a higher dose level. The 1,2,3,4-TCDD compound did not
increase the incidence of malformation at any dose level. Oral administration of 5
or 20 mg/kg per day of OCDD to pregnant mice did not alter fetal development. In
summary, related dibenzo-p-dioxins were relatively nontoxic and were not
teratogenic at the doses studied.
CARCINOGENICITY
Several studies of rats and one study of Swiss mice demonstrated an increased
incidence of neoplasms in animals exposed to 2,3,7,8-TCDD (Van Miller, Lahch,
and Allen 1977; Kociba et al. 1978; Toth et al. 1979). Van Miller and co-workers
exposed rats to diets containing the dioxin at concentrations of 1, 5,50, or 500 ppt,
or 1,5, 50, 500, or 1000 ppb. In this study, the overall incidence of tumors in the
experimental groups was 38 percent, with no neoplasms observed in the 1 ppt
group. As indicated in Table 44, among the 23 animals with tumors, 5 had two
primary neoplastic (cancerous) lesions. Ingestion by rats of 0.1 Mg/kg per day
2,3,7,8-TCDD for two years caused an increased incidence of hepatocellular
carcinomas and squamous cell carcinomas of the lung, hard palate/nasal
turbinates, or tongue, and a reduced incidence of tumors of the pituitary, uterus,
mammary glands, pancreas, and adrenal glands (Kociba et al. 1978). Figures 61
and 62 illustrate the morphology of some of these lesions. In a recent study with
Swiss mice, Toth et al. (1979) showed that 2,4,5-trichlorophenoxyethanol and
2,3,7,8-TCDD enhanced liver tumors in male mice in a dose-dependent fashion. In
this study, the increase in liver tumors was statistically significant only at 2,3,7,8-
TCDD doses greater than 0.112 /jg/kg.
Multiple studies have examined the effects of 2,3,7,8-TCDD administered in
combination with other known carcinogens in experimental animal test systems.
Two studies used the two-stage tumorigenesis assay of mouse skin (Digiovanni et
al. 1977; Berry et al. 1978). Berry and co-workers noted that a dose of 0.1 /Jg
2,3,7,8-TCDD twice weekly was not sufficient to promote skin tumors in mice
treated with 7,12-dimethylbenz(a) anthracene (DM BA). Digiovanni found that at
doses of 2 fj.g per mouse given concurrently with DMBA, the number of tumors
observed increased slightly. These data suggest that 2,3,7,8-TCDD is a weak tumor
initiator in the two-stage system of mouse skin tumorigenesis. In a more recent
study, Digiovanni et al. (1979) found that 2,3,7,8-TCDD could strongly inhibit the
initiation of skin tumors by DMBA in female CD-I mice. In a study with mice that
were genetically nonresponsive to the known carcinogen, 3-methylcholanthrene
(MCA), exposure to 2,3,7,8-TCDD markedly increased the carcinogenic index of
MCA when the compounds were administered simultaneously (Kouri et al. 1978).
These data imply that the dioxin could act as a potent cocarcinogen.
GENOTOXICITY
Only four of the dibenzo-p-dioxins have been subjected to genotoxicity testing.
These are unsubstituted dibenzo-p-dioxin, the 2,7-dichloro-isomer, 2,3,7,8-
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TCDD, and OCDD (Wassom, Huff, and Loprieno 1978). As expected, 2,3,7,8-
TCDD has been the most extensively tested, but results of these studies are
inconclusive. Information implicating 2,3,7,8-TCDD as a mutagen is scarce and
conflicting. Mammalian studies with dibenzo-p-dioxin derivatives have been
infrequent. To date, 2,3,7,8-TCDD has shown negative results when tested for
dominant lethal effects in rats and weakly positive results when tested for the ability
to produce chromosomal abberations in bone marrow cells of rats (Khera and
Ruddick 1973; Green, Moreland, and Sheu 1977).
TABLE 44. SUMMARY OF NEOPLASTIC ALTERATIONS OBSERVED
IN RATS FED SUBACUTE LEVELS OF 2,3,7,8-TCDD FOR 78 WEEKS3
Level of No. of animals
2,3,7,8-TCDD with neoplasms'1 No. of neoplasms
Diagnosis
0
1 pptc
5 ppt
0
0
5
0
0
6
50 ppt
500 ppt
1 ear duct carcinoma
1 lymphocytic leukemia
1 adenocarcinoma (kidney)
1 malignant histiocytoma
(pentoneal)d
1 angiosarcoma (skin)
1 Leydig cell adenoma
(testes)
1 fibrosarcoma (muscle)
squamous cell tumor (skin)
astrocytoma (brain)
fibroma (striated muscle)
carcinoma (skin)
adenocarcinoma (kidney)
sclerosing seminoma
(testes)
ppbe
5 ppb
10
1 cholangiocarcinoma (liver)
1 angiosarcoma (skin)
1 glioblastoma (brain)
2 malignant histiocytomas
(peritoneal)d
4 squamous cell tumors
(lung)
4 neoplastic nodules (liver)
2 cholangiocarcinomas(liver)
a—Source: Van Miller, Lalich, and Allen 1977
b—10 animals per group
c—1 ppt = 10~l2g 2,3,7,8-TCDD/g food
d—Metastases observed
e—1 ppb = 1CT9g 2,3,7,8-TCDD/g food.
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Mutagenicity
Table 45 summarizes the results of studies of the mutagenic effects of dioxins.
None of the Salmonella strains capable of detecting base-pair substitutions were
positive when tested with 2,3,7,8-TCDD. Some investigations have obtained
positive responses in Strain TA 1532, which detects frameshift mutations.
. •*»
Fat
Droplets
Cancer
Cells
Figure 61. Lesion classified morphologically as hepatocellular carcinoma in liver
of rat given 0.1 M9 of 2,3,7,8-TCDD/kg per day. Note adjacent fibrosis,
inflammation, and fatty infiltration on left H & E stain. X200.
Source: Redrawn from Kociba et al. 1978.
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Keratinized
Material
Figure 62. Lesion within lung of rat given 0.1 M9 of 2,3,7,8-TCDD/kg per day.
Classified morphologically as squamous cell carcinoma. Note accumulation
of keratinized material within lesion. H & E stain. X100.
Source: Redrawn from Kociba et al. 1978.
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TABLE 45. MUTAGENICITY OF DIOXIN COMPOUNDS IN SALMONELLA TYPHIMURIUM*
Strains detecting base-pair substitutions6
Dioxin isomer G46 TA1530 TA1535 TA100
2,3,7,8-TCDD o o - o
00-0
o - o o
- - o o
OCDD - - o o
Dibenzo-p-dioxin o o - -
Strains detecting frameshiftsb
TA1531 TA1532 TA1534 TA1537 TA1538
0 - 0 - -
o o o o -
o + o o o
7 + ? 0 0
? ? 0 0
O O 0
Reference
McCann 1975
Nebert 1976
Hussam 1972
Seller 1973
Seiler 1973
Commoner 1976
a—Source Wassom, Huff, and Loprieno 1978
b—Key o = not tested, - = negative results, + = positive results, ? = doubtful mutagen Results obtained with different experimental protocols.
-------
Hussain et al. (1972) report the following results of mutagenicity studies with
2,3,7,8-TCDD (99 percent) on three bacterial systems:
1. 2,3,7,8-TCDD significantly increased the incidence of reverse mutations
from streptomycin-dependence to streptomycin-independence in the
bacteria Escherichia coli SD-4 treated with 2 Mg/ml 2,3,7,8-TCDD. This
was the only concentration at which mutations were clearly observed.
2. Evaluation of reverse mutation from histidine-dependence to histidine-
independence in Salmonella typhimurium strains TA 1532 and TA 1530
indicated that 2,3,7,8-TCDD was positive in TA 1532 but negative in TA
1530. This finding indicates that the dioxin may act as a frameshift
mutagen. ICR-170 was used as a positive control in the test with 1532, but
no positive or negative controls were tested with TA 1530
3. Slight prophage inductions in Escherichia coli K-39 were observed,
although data were difficult to evaluate because the DMSO solvent used in
this test caused cellular effects on its own.
Seller (1973) studied the effects of 2,3,7,8-TCDD and OCDD in several strains of
Salmonella typhimurium. The 2,3,7,8-TCDD was strongly mutagenic only in
strain TA 1532, whereas the OCDD was questionably mutagenic in strains TA
1532 and TA 1534. McCann (1976) obtained no positive mutagenic responses in
several Salmonella strains exposed to 2,3,7,8-TCDD, including TA 1532.
Commoner (1976) demonstrated that unsubstituted dibenzo-p-dioxin was
nonmutagenic in four strains of Salmonella typhimurium.
Khera and Ruddick (1973) performed dominant lethal studies with 2,3,7,8-
TCDD. Groups of male Wistar rats were dosed orally with 4, 8, or 12 yug/kg per
day for 7 days before they mated. Although the incidence of pregnancies from all
matings was reduced, there was no evidence of induction of dominant lethal
mutations during postmeiotic phases of spermatogenesis.
Cytotoxicity
Highly purified samples of 2,4,5-T and 2,3,7,8-TCDD were evaluated for
cytological effects in the African Blood Lily plant (Jackson 1972). The tests
included treatments involving both compounds in varying proportions. In contrast
to a no-effect result with a highly purified sample of 2,4,5-T, dramatic inhibition of
mitosis was observed in cells exposed either to a 10'4 molar solution of 2,4,5-T
containing 0.2 to 1.0 Mg2,3,7,8-TCDDperliterortoa lO'4 molar solution of 2,4,5-
T containing an unknown level of 2,3,7,8-TCDD. Similar results were obtained
when treatments were limited to 2,3,7,8-TCDD alone. These treatments also
induced formation of dicentric bridges and chromatin fusion, with formation of
multinuclei or a single large nucleus. Because these effects were not evident in the
pure 2,4,5-T sample, Jackson concluded that the cytological effects were due to the
2,3,7,8-TCDD contaminant.
Tests for cytological effects in a wild type Drosophila fly were conducted with
2,4,5-T containing less than 0.1 ppm 2,3,7,8-TCDD (Davring and Summer 1971).
Twenty-four hours after eclosion the adult flies were exposed to 250 ppm 2,4,5-T in
their food. Results indicated that this formulation affected early oogenesis and
caused sterility. It is not stated unequivocally that the observed sterility was of
genetic origin.
In an animal study (Greig et al. 1973), male Portion rats were treated with single
oral doses (50 to 400 yug/kg) of 2,3,7,8-TCDD dissolved in either dimethyl
sulfoxide or arachis (peanut) oil. In the rat livers, parenchyma! cell structures were
altered and many cells were multinucleated. No mitoses were observed, and there
were occasional pyknotic nuclei. The investigators postulate that 2,3,7,8-TCDD
interfered with the capacity of the liver cells to maintain their correct morphology
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and thus led to death or structural disorganization. Similar results have been
obtained by others (Buu-Hoi et al. 1971; Kimbroughet al. 1977). Vos et al. (1974)
suggest that 2,3,7,8-TCDD could be a hepatocarcinogen because of its specific
cytological effects on the proliferating cells of the liver.
Chromosomal abberations in bone marrow cells of 2,3,7,8-TCDD-treated
Osborne-Mendel rats have also been reported (Green, Moreland, and Sheu 1977).
No chromosomal abberations or cytogenetic damage was found, however, in bone
marrow of male Osborne-Mendel rats treated with 2,7-di-CDD or unsubstituted
dibenzo-/?-dioxin (Green and Moreland 1975).
2,3,7,8-TCDD may be mutagenic to humans. Chromosomal abnormalities have
been reported in in vitro cytogenetic studies of human lymphocytes exposed to 10 -7
to 10-4m-molar solutions of 2,4,5-T that contained 0.09 ppm 2,3,7,8-TCDD (U.S.
EPA 1978h). Breaks, deletions, and rings were observed. Chromatid breaks
increased with increasing concentrations of 2,4,5-T. It was not possible to
distinguish whether this was a toxic effect or a potential genetic effect.
Pathophysiology
Many investigators have tested apparently logical mechanisms of action for
2,3,7,8-TCDD toxicity. For the most part, these investigations have served only to
disprove proposed mechanisms of action (Beatty et al. 1978; Neal 1979). The
following proposed mechanisms for toxicity induced by 2,3,7,8-TCDD have been
disproved:
• Inhibition of protein synthesis
• Inhibition of DNA synthesis
• Inhibition of mitosis
• Inhibition of oxidative phosphorylation
• Interference with the action of thyroxine
• Interference with glucocorticoid metabolism
• Increased serum ammonia levels
• Depletion of reduced pyridine nucleotides
• Production of superoxide anion
• Decreased hepatic ATP content
• Impairment of hepatic mitochondrial respiration
The most promising explanations for at least the first step in the mechanism of
2,3,7,8-TCDD toxicity result from studies of hepatic ATPase activities (Jones
1975; Madhukar et al. 1979b). Jones administered 200 ^ig/kg of the dioxin to
male albino rats, then sacrificed groups of animals at 24 hours and at 3, 5, 6, 8, 34,
and 42 days. Hematoxylin and eosin stains of liver sections showed no
abnormalities in the groups sacrificed in the 24-hour to 8-day intervals; however, in
the remaining two groups (34 and 42 days) the liver sections showed centrilobular
zone necrosis. As early as 3 days after exposure, a significant change in the pattern
of the ATPase reaction was seen in all animals studied. In an area five to six cells
deep around the central vein, there was no reaction along the canalicular borders of
the parenchymal cells. Similar results were obtained by Madhukar, who studied
Na-, K-, and Mg-ATPase activities in hepatocyte surface membranes isolated from
male rats given 10 or 25 mg/kg 2,3,7,8-TCDD. As early as 2 days after
administration of the dioxin, all of the ATPase activities were depressed in treated
animals. A dose-response relationship was observed only for depression of Mg-
ATPase activity. In further studies, Madhukar demonstrated that ATPase
depression was not produced by in vitro exposures to 2,3,7,8-TCDD.
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EPIDEMIOLOGICAL STUDIES AND CASE REPORTS
The most notable human exposures to 2,3,7,8 tetrachlorodibenzo-p-dioxin have
occurred through accidental releases in chemical factories, or by exposure to
contaminated materials or areas. Most of the studies reported in the literature, such
as those cited below, are investigations of the effects of such exposures.
General Acute Toxicity
The immediate results of dioxin exposure are burning sensations in eyes, nose,
and throat; headache; dizziness; and nausea and vomiting (U.S. NIEHS IARC
1978). Itching, swelling, and redness of the face may occur just prior to chloracne.
Chloracne, similar to acne vulgaris, is one of the most consistent and prominent
features of dioxin exposure, occurring within weeks of initial exposure (May 1973;
Oliver 1975; Poland et al. 1971). Mclnty (1976) showed that as little as 20 Mg of
2,3,7,8-TCDD on the skin can lead to chloracne development. Chloracne may
appear fist on the face and then spread to the arms, neck, and trunk (U.S. NIEHS
IARC 1978; May 1973). Other symptoms of exposure include arthralgias (pains in
the joints without associated arthritic changes), extreme fatigue, insomnia, loss of
libido, irritability, and nervousness (Ensign and Uhi 1978; U.S. NIEHS IARC
1978). High levels of blood cholesterol and hyperlipoproteinaemia may also
develop (Oliver 1975).
Other effects, which may be delayed or immediate, are porphyria cutaneatarda,
hepatic dysfunction, hyperpigmentation, and hirsutism (U.S. NIEHS IARC 1978).
Disorders of the cardiovascular, urinary, respiratory, and pancreatic systems
(Goldman 1973), along with disorders of fat and carbohydrate metabolism also
have been found (U.S. NIEHS IARC 1978). Emotional disorders, difficulties with
muscular and mental coordination, blurred vision, and loss of taste and smell also
may occur (Oliver 1975).
Several deaths related to 2,3,7,8-TCDD have been recorded, some due to liver
damage and others to chronic exposure to the chemical. Additionally, symptoms
such as chloracne can be passed by an exposed person to close associates such as
family members through clothing, hands, or other close contact (Mclnty 1976).
General Chronic Toxicity
Poland etal. (1971) studied possible toxic effects on 73 male workers in a factory
producing the 2,3,7,8-TCDD-contaminated pesticide 2,4,5-T. The workers were
classified according to job location. The medical or lexicological symptoms were
grouped into three categories: 1) chloracne and mucous membrane irritation, 2)
hepatotoxicity, neuromuscular symptoms, psychological alterations, and other
systemic symptoms, and 3) porphyria cutanea tarda (PCT). Of the 73 subjects, 66
percent experienced some degree of chloracne, 18 percent of which was classed as
moderate to severe. The presence of hyperpigmentation and hirsutism correlated
with the severity of the acne. Among maintenance men, who were subject to the
greatest exposure, the acne was more severe than that of administrative personnel,
whose exposure was minimal. Urinary porphyrin values, although within normal
limits, were elevated in the maintenance men as compared with the other
workers. Although 2,3,7,8-TCDD and other chemicals produced in 2,4,5-T
synthesis may be hepatotoxic in humans, demonstrable chemical liver dysfunction
among workers in this plant was minimal.
The toxic effect of 2,3,7,8-TCDD on three young laboratory scientists was
reviewed in a case study by Oliver (1975). Two of the subjects worked with the
dioxin for approximately 6 to 8 weeks, and the third for approximately 3 years
before onset of symptoms. The latter scientist worked only with a diluted sample of
the material, whereas the other two worked on the synthesis of dioxins. Chloracne
was the first symptom experienced by two of the scientists. Two of them also
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suffered from delayed reactions, experiencing abdominal pain, headache, excessive
fatigue, uncharacteristic episodes of anger, diminished concentration, other
neurological disturbances, and hirsutism approximately 2.5 years after exposure.
None of the scientists showed liver damage or porphyrinuria; all three showed
elevated serum cholesterol levels, evidence of hypocholesterolemia, and
hyperlipoproteinaemia. No other biochemical abnormalities were noted. Over a
period of 6 months (after the onset of the delayed symptoms), the symptoms
subsided. All three scientists were aware of the danger involved in the substance
with which they were working; they wore protective clothing, gloves, and masks,
and worked under a vented hood. The author speculated that the exposures must
have been extremely low.
Accidental release of 2,3,7,8-TCDD occurred in an explosion at a chemical plant
in Derbyshire, England. This exposure of workers resulted in 79 cases of chloracne
recorded approximately 3 weeks after the explosion (May 1973). Young men with
fair complexions were affected first, but the symptoms persisted longer in sallow-
skinned men ages 25 to 40. Chloracne was present, in order of prevalence, on the
face, extensor aspects of arms, lateral aspects of thighs and calves, back, and
sternum. Most workers recovered in 4 to 6 months. Of 14 employees who were
present during the explosion, 13 showed abnormal liver function and 9 developed
chloracne. Those with chloracne had handled pipes, joints, and cables with bare
hands and thus may have absorbed the dioxin through the skin; this finding
suggests that excretion of absorbed dioxin or its products may occur through
facial pores.
Jirasek et al. (1973, 1974, 1976) cite many studies done on 80 industrial workers
in Czechoslovakia who showed signs of intoxication from dioxin formed as a
byproduct in production of the sodium salts of 2,4,5-T and pentachlorophenol.
Symptoms included 76 cases of chloracne, ranging from mild to so severe that it
covered the entire body and left scars. Twelve workers had hepatic lesions with
symptoms of porphyria cutanea tarda. Symptoms in 17 of the workers included
polyneuropathy, psychic disorders, weakness and pain in the lower extremities,
somnolence or insomnia, excessive perspiration, headache, and disorders of the
mental and sexual functions. One worker suffered and died from severe
atherosclerosis, hypertension, and diabetes; two workers died from bronchogenic
carcinoma (lung cancer) (ages 47 and 59). Periods of latency differed; in some
instances severe dermatological and internal damage developed after brief
exposure, whereas in others apparently long-term and massive exposure caused
only mild symptoms.
Another study (Poland and Kende 1976) deals with 29 workers who were
accidentally exposed to 2,3,7,8-TCDD. Of the 29, all contracted chloracne, 11
developed porphyrinuria, and several developed porphyria cutanea tarda. The
workers also showed signs of mechanical fragility, hyperpigmentation, hirsutism,
and photosensitrvity of the skin, in which sunlight exposure caused blistering.
Measures were taken at this plant to decrease 2,3,7,8-TCDD production and
worker exposure. Within 5 years there was no evidence of porphyria or severe acne,
and severity of the other symptoms was also reduced. In all cases reviewed, an acute
exposure to dioxins resulting in chloracne and other acute symptoms and followed
by a period of nonexposure to the substance resulted in the disappearance or
diminution of the symptoms.
In early May of 1971, an accidental poisoning incident killed or intoxicated
many horses and other animals that came in contact with the soil of an arena
sprayed with contaminated oil. Investigators identified 2,3,7,8-TCDD and
polychlorinated biphenyls as the causative agents (Carter et al. 1975; Kimbrough et
al. 1977). A six-year old girl who played in the arena soil developed symptoms of
headache, epistaxis (nosebleed), diarrhea, and lethargy. In August 1971, she
developed hemorrhagic cystitis (inflammation of the urinary bladder). The
patient's symptoms resolved in 3 to 4 days and did not recur. Proteinuria and
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hematuria (protein and blood in the urine) disappeared within 1 week of onset. A
voiding cystogram obtained 3 months later appeared normal; however, cystoscopy
demonstrated numerous punctate hemorrhagic areas, especially in the trigone
region of the bladder. The patient was reexamined 5.3 years after dioxin exposure.
Physical examination was performed, as well as urinalysis, a voiding cystogram, an
intravenous pyelogram, renal function chemistries, an electrocardiogram, stress
test, liver-function tests, uroporphyrin excretion, and thyroid-function studies.
Results of all tests were essentially within normal limits (Beale et a). 1977). Three
other individuals exposed to the arena developed recurrent headaches, skin lesions,
and polyarthralgia (Kimbrough et al. 1977).
In another sprayed arena, two three-year-old boys developed small, pale,
nonpruritic, firm papules covered by blackheads on the exposed skin surfaces.
These symptoms arose 1.5 months after the spraying. They increased in severity
and lasted more than a year before gradually subsiding (Carter et al. 1975).
Perhaps the most publicized incident of dioxin poisoning was that in Seveso,
Italy. On July 10, 1976, at a plant where trichlorophenol was manufactured, an
accident created temperature conditions ideal for formation of 2,3,7,8-TCDD
(Zedda, Circla, and Sala 1976). Trichlorophenol crystals and 2,3,7,8-TCDD in the
form of dust were spread over the area (Hay 1976a). In addition to 170 plant
employees, approximately 5000 persons were exposed (Zedda, Circla, and Sala
1976).
Shortly after the accident, cases of chloracne were reported. Over the ensuing
years more than 134 confirmed cases of chloracne have occurred in children, some
of whom had not been in the area during July and August 1976. These latter cases
indicate that enough dioxin persisted in the environment several months after the
accident to cause the chloracne (Zedda, Circla, and Sala 1976). Reports of
disorders among the 170 workers exposed include 12 cases of chloracne in directly
contaminated workers, 29 cases of hepatic insufficiency, 28 cases of chronic
bronchitis, 17 cases of arterial hypertension, 9 cases of coronary insufficiency, 8
cases of muscular asthenia (weakness), and 3 cases of reduced libido (Zedda,
Circla, and Sala 1976). Reported symptoms occurring among the exposed
residents include chloracne, nervousness, changes of character and mood,
irritability, and loss of appetite. Legal and illegal abortions were estimated at 90,
and there were 51 spontaneous abortions (U.S. EPA 1978h).
Several additional followup studies of the initially identified cohort have been
reported recently (Reggiani 1978, 1979a,b; Pocchiari, Silano, and Zampieri 1979).
In 1978, Reggiani reported that chloracne had appeared almost only in children
and young people. These cases tended to be mild, and spontaneous healing
occurred in most. Transient lymphocytopenia and liver function abnormalities
were detected. Reports at that time indicated no overt pathology of the liver,
kidney, blood, reproductive organs, central and peripheral nervous systems, or
metabolism of carbohydrate, fat or porphyrin. In 1979, Reggiani reported that the
incidence of chloracne remained between 0.6 and 1.5 percent in the surveyed
population and other toxic manifestations initially observed remained at
subclinical levels.
Pocchiari, Silano, and Zampieri (1979) reported a somewhat more detailed
followup of the cohort. In the cohort with highest exposure, chloracne was
identified in approximately 13 percent of the screened population. About 4 percent
of the workers from the plant (Pocchiari sets the number at 200) showed signs and
symptoms of polyneuropathy. Subclinical peripheral nerve damage, confirmed by
nerve conduction studies, was also observed fairly frequently in nonoccupationally
exposed groups, and the incidence ranged from 1.2 to 4.9 percent in the screened
population. Of note, there were no documented immunologic alterations in the
exposed population. Eight percent of the screened population showed
hepatomegaly of undetermined etiology, and some of the screened population
showed elevated levels of liver transaminases.
225
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The long-term effects of exposure to 2,3,7,8-TCDD in Seveso are not clear at this
time. An epidemiologic survey now in progress includes general and specialized
medical examinations, laboratory tests, and data on the outcome of pregnancies.
Data will be collected overa period of 5 years. Cancer registries, hospital discharge
forms, notifications of infectious diseases, and birth and death certificates will be
used to detect any abnormalities of the health of the community (Fara 1977).
Fetotoxicity and Teratogenicity
Hexachlorophene (HCP) is a derivative of 2,4,5-TCP that has been used as an
antibacterial agent for the past 20 years. Although there are no reports of 2,3,7,8-
TCDD contamination in HCP, this drug has been shown to cause fetal
malformations, some of which are severe (U.S. NIEHS IARC 1978). A study of
mothers who were nurses exposed to hexachlorophene soap during early
pregnancy showed that of 65 children born, 5 had severe and 6 had slight
malformations. One slight malformation was observed in 68 children of an
unexposed control group. Five babies died who had been washed more than three
times with 3 percent hexachlorophene in a hospital. Autopsies revealed
considerable brain damage in each case. In 1972, many infant fatalities were
reported in France. The cause was cited as a new talc powder called "Bebe," which
contained 6 percent HCP (dioxin content, if any, is unknown) (Mclnty 1976).
It is reported that the local spontaneous abortion rate has increased to twice the
national level in Italy since the chemical contamination of Seveso in 1976, and that
similar results have occurred in Vietnam since the spraying of Herbicide Orange
(Nature 1970). Unfortunately, doctors in Vietnam are unable to document
increased abortion and birth defects because of inadequate medical records (U.S.
EPA 1978a).
In the sprayed areas of Vietnam, doctors have cited increased incidences of
babies being born with extra fingers or without fingers, hands, or feet (Lawrence
Eagle Tribune 1978). Recently, a group of U.S. military veterans who were in
South Vietnam at the time of the spraying have reported birth defects in their
offspring similar to those reported in South Vietnam (Ensign and Uhi 1978;
Lawrence Eagle Tribune 1978; Peracchio 1979).
An EPA study has been done on the relationship of dioxin-containing herbicides
to miscarriages; specifically the study concerns the relationship between spraying
2,4,5-T on forested areas of Oregon and miscarriages among women living in
Alsea, a town near a sprayed area. Scientists from Colorado State University and
the University of Miami medical school compared miscarriages in the Alsea basin
with those in a control area in rural eastern Oregon. The miscarriage rate in the
Alsea area was significantly higher than in the control area, where 2,4,5-T was not
sprayed. Miscarriage rates peaked dramatically in June of each of the 6 years
studied, occurring 2 or 3 months after the yearly spring applications. From 1972
through 1977 the spontaneous abortion indexes in June were 130 per 1000 births in
Alsea and 46 per 1000 in the control area. Although these data do not prove a cause
and effect relationship, they are highly suggestive (Cookson 1979).
A recent study deals with the relationship of neural-tube defects in New South
Wales and annual usage rates of 2,4,5-T in the whole of Australia (Field and Kerr
1979). Table 46 gives data showing the annual New South Wales combined birth
rates of anencephaly (congenital absence of the cranial vault), and meningo-
myelocele (defect through which part of the spinal cord communicates with the
environment), together with data on the usage of 2,4.5-T in Australia in the
previous year. The plot in Figure 63 indicates linear correlation. Highest rates on
neural-tube defects occurred for conceptions during the summer months, and
maximum spraying of 2,4,5-T in New South Wales occurs during the summer
months. Again, although these data are suggestive, they do not prove a cause and
effect relationship. The linear correlation disappeared in 1975 and 1976;
226
-------
TABLE 46. COMBINED RATE OF NEURAL-TUBE DEFECTS
IN NEW SOUTH WALES AND PREVIOUS-YEAR USAGE OF 2,4,5-T
IN AUSTRALIA3
Neural-tube defects Usage of 2,4,5-T in Australia
in New South Wales in previous year
Year (cases per 1000 births) (metric tons)b
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1.72
1.77
1 93
1.83
2.13
2.37
1.88
2.15
2.19
2 27
2.03
2.30
90
105
188
213
201
282
170
256
241
287
466
482
a—Source. Field and Kerr 1979
b—2,4,5-T acid in equivalent metric tons.
monitoring of 2,4,5-T herbicide was established in Australia to ensure that
concentrations of 2,3,7,8-TCDD remain below 0.1 ppm.
Nelson et al. (1979) report a retrospective study of the relationship between use
of 2,4,5-T in Arkansas and the concurrent incidence of facial clefts in children.
Occurrences of facial cleft generally increased with time; however, no significant
differences were found in any of the study groups. The authors conclude that the
general increase in facial cleft incidence in the high- and low-exposure groups
resulted from better case finding rather than from maternal exposure to 2,4,5-T.
Among 182 babies delivered in Seveso in the 2 months after the accident, only 16
birth anomalies were found. This level is not significantly higher than the national
level. Women in early stages of pregnancy when the accident happened were not
studied in this survey (U.S. EPA 1978a).
Carcinogenicity
Ton That et al. (1973) report an increase in the proportion of primary liver cancer
among all cancer patients admitted to Hanoi hospitals during the period 1962 to
1968; this increase is relative to the period 1955 to 1961, just before the spraying of
Herbicide Orange began.
Theiss and Goldmann (1977) trace 4 cancer deaths out of 15 deaths occurring in
53 workers exposed to 2,3,7,8-TCDD after a manufacturing accident in a TCP
plant in Ludwigshafer, Germany, in 1953. A followup study is in progress.
Two studies show an increased incidence of malignant mesenchymal soft-tissue
tumors in persons exposed to phenoxy acids or chlorophenols (Hardell and
Sandstrom 1978; Hardell 1979). In the 1978 study, 52 patients with soft-tissue
sarcomas and 205 matched controls were investigated in a cohort study. The
incidence of exposure was 19/52 among the tumor patients and 19/206 in the
tumor-free controls (p < 0.001). Relative risks were determined to be 5.3 for
227
-------
8
in
8
CO
8
o
in
tM
O
O
c
o
in
•*
cs"
q
CO
q
c-i
in
d
sujjjq oOOL/saseo 'Q1N
o
in
8
o
in
Figure 63. Linear correlation of New South Wales rate for neural-tube defects
with previous year's usage of 2,4,5-T in Australia.
Source: Field and Kerr 1979.
228
-------
exposure to phenoxy acid and 6.6 for exposure to chlorophenols. In the 1979 study,
Hardell prospectively studied patients with histocytic, malignant lymphoma. In the
first phase of the study, 14 of 17 patients reported occupations consistent with the
possibility of exposure to the chemicals under study, and 11 patients reported
definite exposure to phenoxyacetic acids or chlorophenols. The median latent
period between exposure and tumor detection in this group was 15 years.
Rappe (1979) has reported an increased incidence of primary liver cancer in
members of the Vietnamese population exposed to Herbicide Orange.
Mutagenicity
Chromosomal analyses in Seveso have shown an increase in chromosomal
lesions in males and females aged 2 to 28 years. These lesions consist of
chromosomal gaps, and chromalid and chromosomal breaks and rearrangements.
Cytogenetic studies indicate chromosomal damage to cells in maternal peripheral
blood and in placental and fetal tissues studied following therapeutic abortions
(U.S. EPA 1978h).
In similar analyses, Tenchini et al. (1977) found a higher number of structural
aberrations in the fetal tissues than in the maternal blood samples of fibroblast cells
from adult tissues, but the frequency of these aberrations did not appear to be
greater than expected to occur spontaneously in cultures of comparable cell types.
Tenchini et al. point out that these preliminary findings do not indicate whether the
higher frequencies of chromosome aberrations in fetal tissues were due to
chromosome damage caused by 2,3,7,8-TCDD exposure.
In contrast, the chromosomes of peripheral blood cells from 90 workers at the
chemical plant at Seveso showed no abnormalities; the same results were obtained
in a sampling of the most severely exposed residents of the area (Wassom 1978).
Czeizeland Kiraly (1976) compared the frequency of chromosome aberrations in
the peripheral lymphocytes of 76 workers employed at a herbicide-producing
factory in Budapest with those of 33 controls. Among these workers, 36 were
exposed to 2,4,5-trichlorophenoxyethanol (TCPE) or Klorinol and 26 to Buvinol.
The remaining 14 workers had never been engaged in the production or use of
either herbicide. The 2,3,7,8-TCDD concentration in the herbicide products is
reported to be either less than 0.1 mg/kg or not more than 0.05 mg/kg. The
frequency of chromatid-type and unstable chromosome aberrations was higher (p
< 0.01) in the factory workers than in the controls, regardless of involvement in
production of the herbicide. Aberrations were more frequent in workers preparing
TCPE and Buvinol than in other factory workers, but the difference was significant
only for the chromatid-type effect.
229
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SECTION 7
ENVIRONMENTAL DEGRADATION
AND TRANSPORT
This section addresses the fate of dioxins once they are released to the
environment. Subsections on biodegradation and photodegradation deal with
recent literature relating to biochemical and physical actions of the environment as
they affect the integrity of the dioxin structure. Subsections on physical and
biological transport deal with the movement of dioxins in soil, water, and air and
with the uptake of dioxins by plants and their fate in animals at various trophic
levels.
BIODEGRADATION
In assessment of the persistence of a substance in the environment, the
susceptibility of that substance to biodegradation* is a primary concern. Several
studies on the biodegradability** of dioxins are described in the literature. The
investigations show that dioxins exhibit relatively strong resistance to
biodegradation, though they may not necessarily be totally recalcitrant. Most of
the work has focused on 2,3,7,8-TCDD because of its extreme toxicity. This dioxin
has been studied in both aqueous and soil environments, and results have been
somewhat equivocal. Only one study (Kearney et al. 1973) has examined the
biodegradability of another dioxin, 2,7-DCDD. Data from this study indicate that
this dioxin can be at least partially degraded in soils. Several dioxin
biodegradation studies are described in the following paragraphs, but due to recent
information concerning problems of extracting dioxins from the test soils, it must
now be concluded that the biodegradability of dioxins has not been demonstrated.
Approximately 100 strains of microbes that had previously shown the ability to
degrade persistent pesticides were tested for their ability to degrade 2,3,7,8-TCDD.
After incubation, extracts from microorganisms were prepared and analyzed for
metabolites by thin-layer chromatography. Of the strains tested, five showed some
ability to degrade the dioxin.
Some studies, as described in the next three paragraphs and other places within
this compilation, have been conducted with MC-labeled 2,3,7,8-TCDD. Dow
Chemical Company points out that 14C-labeled experiments are limit-producing
only and are not quantitative in spite of some data being reportd to two significant
figures (Crummett 1980).
Ward and Matsumura studied the biodegradation of MC-labeled 2,3,7,8-TCDD
in Wisconsin lake waters and sediments and reported in 1977 that the dioxin may
be genuinely metabolized in aqueous systems, but that the rate is very low. They
concluded that there is an optimum time for microbial degradation, probably 1
month, and that during this period, available 2,3,7,8-TCDD is degraded while the
nonavailable fraction is bound to the water sediments. The limited degradation of
*Biodegradation the molecular degradation of an organic substance resulting from the complex actions
of living organisms. A substance is said to be biodegraded to an environmentally acceptable extent when
environmentally undesirable properties are lost. Loss of some characteristic function or property of a
substance by biodegradation may be referred to as biological transformation. (CEFIC 1978)
* Biodegradability. the ability of an organic substance to undergo biodegradation
230
-------
2,3,7,8-TCDD is favored by the presence of sediment, microbial activity, and/or
organic matter in the aqueous phase. The observed half-life of 2,3,7,8-TCDD in
sediment-containing lake waters was 550 to 590 days; the half life in waters without
sediment was longer.
Kearney and co-workers studied two types of soil, which were incubated with
2,3,7,8-TCDD at concentrations of 1, 10, and 100 ppm and with l4C-labeled
2,3,7,8-TCDD at concentrations of 1.78, 3.56, and 17.8 ppm (Kearney et al. 1973a).
The two soils were also inoculated with MC-labeled 2,7-DCDD at concentrations
of 0.7, 1.4, and 7.0 ppm. The soil types were Hagerstown silt clay loam, which is
relatively high in organic matter and microbial activity, and Lakeland sandy loam,
which is low in organic matter and microbial activity. Over a 9- to 10-month period,
the soil samples were monitored weekly for evolution of gaseous I4CO 2 as an
indication of microbial degradation of the labeled dioxins.
Very little CO2 was liberated from soils containing either labeled or unlabeled
2,3,7,8-TCDD. In most cases 75 to 85 percent of the dioxin was recovered from
both soil types up to 160 days after addition. No metabolites were found in TCDD-
treated soil after 1 year. About 5 percent of the '4C-2,7-DCDD had degraded to
liberate >4CO2 after 10 weeks. Concentrations of >4C-2,7-DCDD in the soil had a
slight effect on I4CO2 evolution. It was postulated that the decrease in CO2
liberation at the highest level may have resulted from the toxicity of the DCDD
isomer to the microbes at this concentration. Evolution of 14CO2 was significantly
higher in the Lakeland soil than in the Hagerstown soil. Analysis of DCDD-treated
soil extracts also revealed the presence of metabolites, but the major metabolite
could not be identified.
In the same study, incubation of a clay loam (with relatively low organic matter)
to which 14C-2,3,7,8-TCDD had been applied led to liberation of a "very small
amount of I4CO2" after 2 weeks.
The U.S. Air Force studied test plots in Utah, Kansas, and Florida to determine
the soil degradation rate of 2,3,7,8-TCDD under field conditions (Young et al.
1976). The three test plots were considered representative of various climatic
conditions and soil types. Herbicide Orange containing 3700 ppb 2,3,7,8-TCDD
was applied to all three plots at a rate of 4480 kg/ hectare. Initial soil concentrations
of the dioxin were not reported for any of the sites. Composite samples from the
upper 15 cm of each soil were taken from time to time after the initial herbicide
application, and analyzed for both the herbicide and 2,3,7,8-TCDD. Results are
presented in Table 47.
From these data and other leaching data, the Air Force concluded that the
disappearance of 2,3,7,8-TCDD was most likely due to degradation by soil
microbes, because dioxin concentrations in the 15- to 30-cm layer indicated that
leaching was insignificant. The Air Force report further stated that dioxin
degradation was most rapid in the Kansas soil (Ulysses silt loam), followed by the
Florida soil (Lakeland sandy loam), and finally the Utah soil (Lacustine clay loam),
but that variations in soil and climate had little overall influence on dioxin
persistence. It was also reported that the initial breakdown rate was rapid, but
decreased substantially over the test period. On the basis of this observation the
investigators speculated that microbial enzymes responsible for herbicide
metabolism and possibly dioxin metabolism are inducible.
In an evaluation of the Air Force studies, Commoner and Scott (1976) came to
different conclusions. After constructing semilogarithmic plots of dioxin
concentrations in soil against days after incorporation of the dioxin, they
concluded: (1) that there was no evidence that the rate of degradation changed with
time; and (2) that degradation appeared to be more rapid in the Florida soil than in
the Kansas soil (opposite of the Air Force conclusion).
In another Air Force study with dioxin-contaminated soil the effects of nutrients
and mixing on 2,3,7,8-TCDD degradation were assessed (Bartleson, Harrison, and
Morgan 1975). Pots containing either test soils or control soils were placed
231
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TABLE 47. CONCENTRATIONS OF HERBICIDE ORANGE AND
2,3,7,8-TCDD IN THREE TREATED TEST PLOTS3
Test plot
Utah
Kansas
Florida
Days after application
282
637
780
1000
1150
8
77
189
362
600
659
5
414
513
707
834
1293
Total herbicide b
(ppm)
8490
4000
2260
2370
960
1950
1070
490
210
40
<1
4897
1866
824
508
438
<10
2,3,7,8-TCDD
(ppb)
15.0
7.3
5.6
3.2
25
c
0.255
c
c
c
0042
0375
0250
0075
0046
c
c
a—Plots treated with 4480 kg herbicide per hectare
b—Composite sample from upper 0 to 15 cm layer of soil
c—Not analyzed
outdoors and in a greenhouse. The soils were analyzed after 9 and 23 weeks. Soils
tested in the greenhouse were moistened with a nutrient solution. The results are
presented in Table 48.
The investigators concluded that the accelerated rate of degredation observed in
soil from the pots in the greenhouse during the first 9-week period was probably
due to increased microbial populations resulting from initial soil aeration and
increased soil temperatures in the pots. Reduction in the rate of breakdown after 9
weeks may have been caused by leaching or entrapment of dioxin in the bottom soil
layer, which had not been mixed. It was also proposed, however, that the nutrient
solution together with light or aeration caused either a direct chemical breakdown
of 2,3,7,8-TCDD in the soil or an increase in microbial populations that
accelerated breakdown. Because green algae were observed on the surface of the
greenhouse pots between tillings, it was also postulated that the algae were partly
responsible for the degradation.
This study was also evaluated by Commoner and Scott (1976), who concluded
that mixing, nutrients, and increased exposure to sunlight did not significantly
enhance degradation of 2,3,7,8-TCDD in soil.
Pocchiari (1978) attempted to stimulate the microbial degradation of 2,3,7,8-
TCDD in samples of Seveso soil contaminated with the dioxin from the 1976
ICMESA accident. The dioxin-contaminated soil samples were either inoculated
with promising microorganisms (according to the previously described results of
Matsumura and Benezet in 1973) or enriched by the addition of organic nutrients.
No positive degradation effects have been found.
232
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TABLE 48. DEGRADATION OF 2,3,7,8-TCDD IN SOIL3
(parts per trillion 2,3,7,8-TCDD)
Length of exposure (weeks)
0 9 23
Controls
Outdoor exposure
Tilled (top layer)
Unfilled
Greenhouse
Tilled (top layer)
Until led
1100-1300
1100
1000
640
810
520
530
460
530
a—Source Bartleson, Harrison, and Morgan 1975.
Investigators from the Microbiological Institute in Zurich, Switzerland, have
found that microbes cannot contribute quickly or efficiently to the
decontamination of soil-bound 2,3,7,8-TCDD, although they might contribute
slowly (Huetter 1980). The latter point is supported by the observation of two polar
bands in thin-layer chromatographs of some microbial incubations. Huetter and
co-workers also have observed that when 2,3,7,8-TCDD is incubated with soil for a
prolonged period of time, it is not as extractable as when it is freshly added to the
soil, indicating that recoverability of the dioxin becomes increasingly more difficult
with time. This information raises questions about the accuracy of work done by
others in the past to measure the soil half-life of 2,3,7,8-TCDD.
Preliminary findings of studies under way in Finland indicate that 2,3,7,8-
TCDD may be slowly biodegraded by anaerobic microorganisms in an organic
matrix used for secondary treatment of chlorophenolic wastewaters from paper-
pulping operations (Salkinoya-Salonen 1979).
Klecka and Gibson (1979) have recently reported that unsubstituted dibenzo-p-
dioxin can be readily metabolized by a mutant strain of Pseudomonas (sp. N.C.I.B.
9816 strain II) when an alternative source of carbon such as salicylate is available.
The dioxin molecule was metabolized first to cis-l,2-dihydroxy-
l,2-dihydrodibenzo[l,4]dioxan (I), which was subsequently dehydrated to yield 2-
hydroxydibenzo[l,4]dioxan (II) as the major metabolite. The authors reported
finding no organisms capable of utilizing dibenzo-p-dioxin as a sole carbon source.
II
PHOTODEGRADATION
Photodegradation is the process of breaking chemical bonds with light. The
process, also known as photolysis, involves the breakdown of a chemical by light
233
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energy, usually in a specific wavelength range. In photodegradation of dioxins, the
ultraviolet wavelengths of light have been shown to be the most effective.
In most photolysis studies, scientists are interested in determining one or more of
the following parameters:
1. Photolysis reaction rates
2. Photolysis reaction products
3. Wavelength(s) required for photolysis
4. Other specific conditions required for photolysis
The photolysis of chlorinated aromatic compounds usually involves loss of a
chlorine molecule to a free radical, or loss through nucleophilic displacement if a
solvent or substrate molecule is present. These mechanisms may be influenced by
the presence of other reagents or the nature of the reaction medium.
Photolysis studies have clearly shown that dioxins may be photolytically
degraded in the environment by natural sunlight. The extent to which this
mechanism actually removes or degrades dioxins in the "real-world" environment
is difficult to assess, but of all the possible natural removal mechanisms, photolysis
appears to be the most significant. It should be noted that photolysis apparently
results in the removal of one or more chlorine atoms from the dioxin molecule.
Removal of chlorine from 2,3,7,8-TCDD may make it less toxic, but it has been
speculated that the basic dioxin structure remains. When penta-CDD is
photodegraded, it may go to a TCDD isomer. (For further discussion see pp. 263-
264 of Section 8.)
Several dioxin photodegradation studies are discussed in the paragraphs that
follow. Major findings from these studies are summarized in Tables 49 and 50.
Crosby et al. (1971) studied photolysis rates of 2,3,7,8-TCDD, 2,7-DCDD, and
OCDD dissolved in methanol. Samples were irradiated with natural sunlight or
artificial sunlight with a light intensity of 100 MW/cm2 at the absorption
maximum of 2,3,7,8-TCDD (307 nm). Irradiation of a single solution of 2,3,7,8-
TCDD in methanol for 24 hours in natural sunlight resulted in complete photolysis
to less-chlorinated dioxin isomers. The degradation of 2,7-DCDD was at least
initially more rapid than that of 2,3,7,8-TCDD. After 6 hours of irradiation in
artificial ultraviolet light, about 30 percent of the 2,7-DCDD remained unreacted
whereas almost 50 percent of the 2,3,7,8-TCDD remained unreacted. The amount
of 2,7-DCDD remaining after 24 hours was not reported. The OCDD was
photolyzed much more slowly than the TCDD or DCDD isomers; after 24 hours,
over 80 percent of the initial OCDD (2.2 mg/liter) remained unreacted. Analysis of
reaction products indicated chlorinated dioxins of reduced chlorine content.
In another study the degradation of OCDD on filter paper was reported as being
more rapid in natural sunlight than in artificial ultraviolet light (Arsenault 1976).
Degradation of OCDD also proceeded more rapidly in the presence of mineral oil
or a petroleum oil solvent than in the absence of oil. When OCDD in oil was
exposed to natural sunlight, 66 percent was decomposd in as little as 16 hours.
When exposed in the absence of oil, only 20 percent was decomposed within 16
hours. No TCDD's were found in the decomposition products.
The same report describes a study of the rate of OCDD degradation on the
surfaces of wooden poles treated with PCP-petroleum and Cellon. Preliminary
results show that the OCDD is rapidly degraded. Breakdown products are not
reported.
In tests involving exposure of a crystalline water suspension of 2,3,7,8-TCDD to
a sunlamp, the insolubility of the dioxin caused difficulties. Irradiation apparently
had no effect on the water suspension. A crystalline state may prohibit the loss of
chlorine or obstraction of hydrogen atoms from each other (Plimmer 1978a).
When a benzene solution of 2,3,7,8-TCDD was added to water stabilized with a
surfactant and irradiated with a sunlamp, the dioxin content was reduced (Plimmer
et al. 1973).
234
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TABLE 49. PHOTODEGRADATION OF 2,3,7,8-TCDD
Physical conditions
TCDD in methanol
TCDD in methanol
TCDD (crystalline) in water
TCDD on soil
TCDD in benzene/water/
surfactant
TCDD crystals on glass plate
TCDD in isooctane and
1 -octanol
TOUD in Herbicide Orange,
on glass
TCDD in commercial Esteron
herbicide, on glass
TCDD in Esteron base, on glass
Light source
Artificial
(100 MW/cm2)
Natural sunlight
Artificial
(sunlamp)
Artificial
(sunlamp)
Natural sunlight
Artificial (G E
RS sunlamp)
Natural sunlight
Natural sunlight
Natural sunlight
Length Amount degraded
of exposure (%) Reaction products
24 h
7 h
NR
96 h
NR
1 4 days
40 min
24 h
6h
6 h
2 h
100
100
0
0
>0
0
50
100
60
70
90
Trichlorodibenzo-p-dioxm
Dichlorobenzo-p-dioxin
NRa
NAb
NR
NR
NR
NR
NR
Reference
Crosby et al. 1971
Crosby et al. 1971
Crosby et al. 1 973
Plimmer et al. 1973
Crosby et al. 1971
Stehl et al. 1973
Stehl et al. 1973
Crosby and Wong 1977
Crosby and Wong 1 977
Crosby and Wong 1 977
(continued)
-------
TABLE 49. (continued)
Physical conditions
TCDD in Herbicide Orange,
on plant leaves
TCDD in Herbicide Orange,
on soil
TCDD on silica gel
TCDD on silica gel
TCDD in Seveso soil with
ethyl oleate-xylene mixture
TCDD in 1 -hexadecylpyndinium
chloride (CPC)
TCDD in sodium dodecylsulfate
(SDS)
TCDD in methanol
Light source
Sunlight
Sunlight
Artificial X
>290 nm
Artificial A.
= 230 nm
Sunlight artificial
(Phillips MLU
300 W)
Artificial
Artificial
Artificial
Length
of exposure
6 h
6 h
6 h
7 days
7 days
7 days
3 days
4 h
4 h
8 h
4 h
8 h
Amount degraded
(%) Reaction products
100
70
10
92 NRa
98 NR
>90 NR
100
>90 NR
=50 NR
=100 NR
=50 NR
=75 NR
Reference
Crosby and Wong 1 977
Crosby and Wong 1 977
Gebefuigi 1977
Gebefuigi 1977
Bertoni 1978
Botre et al. 1978
Botre et al. 1978
Botre et al. 1978
(continued)
-------
TABLE 49. (continued)
Physical conditions Light source
TCDD in Seveso soil/treated Natural sunlight
with aqueous olive oil solution
or olive oil/cyclohexanone
TCDD in emulsifiable silvex Natural sunlight
formulation
TCDD in granular silvex Natural sunlight
formulation
Length
of exposure
9 days
=8 days
=135 days
Amount degraded
(%) Reaction products
>90 NR
50 NR
50 NRa
Reference
Crosby 1978
Nash and Beall 1978
Nash and Beall 1978
a—NR = Not reported
b—NA = Not applicable
-------
TABLE 50. PHOTODEGRADATION OF DCDD AND OCDD
Physical conditions
OCDD in methanol
OCDD on filter paper
OCDD in oil
(mineral or petroleum)
OCDD— no oil
OCDD/benzene-hexane
OCDD/benzene-hexane
OCDD in isooctane
OCDD in 1-octanol
DCDD in methanol
DCDD in isooctane and
1 -octanol
Light source
Artificial UV light
(100 /aw/cm2)
Artificial sunlight
Natural sunlight
Natural sunlight
Natural
Mercury UV lamp
Mercury UV lamp
Artificial UV light
Artificial UV light
Artificial UV light
Artificial UV light
Length
of exposure
24 h
NRa
16 h
16 h
4 h
24 h
18 h
20 h
=6 h
40 mm
Amount degraded
(%)
>20
More rapid in natural
sunlight than artificial
UV light
66
20
70
90
20
6
=70
50
Reaction products
Series of chlorinated
dioxms of decreasing
chlorine content
NR
NR
NR
Hexa-CDD, hepta-CDD,
penta-CDD
Hexa-CDD, hepta-CDD,
penta-CDD, TCDD (trace)
NR
NR
NR
NR
Reference
Crosby et al 1971
Arsenault 1976
Arsenault 1976
Arsenault 1976
Buser 1 976
Buser 1 976
Stehl etal 1973
Stehl et al 1973
Crosby etal 1971
Stehl et al 1973
a—NR = Not reported
-------
In another study when 2,3,7,8-TCDD was applied to dry or moist soil,
irradiation caused no change after 96 hours. Similar results were obtained by
applying this substance to a glass plate and irradiating up to 14 days (Crosby et al.
1971).
Buser (1976) irradiated samples of a solution of OCDD in benzene-hexane for 1
to 24 hours with a mercury ultraviolet lamp. After 4 hours of exposure, 30 percent
of the OCDD remained unchanged; the major reaction products were hexa- and
hepta-CDD'sand trace amounts of penta-CDD's. After 24 hours of irradiation, the
hexa- and hepta-CDD's still constituted the major reaction products, with
significant amounts of penta-CDD's and trace amounts of TCDD's. Only 10
percent of the initial OCDD remained unchanged. It was concluded that since
some commercial products contain up to several hundred ppm of the octa- and
hepta-CDD's, photolytic formation of more toxic polychlorinated dioxins could
have environmental significance.
Exposure of TCDD's and DCDD's in isooctane and 1-octanol to artificial
sunlight (General Electric RS sunlamp) showed that both substances had half-lives
of about 40 minutes in each solvent (Stehl et al. 1973). Analysis of the mixtures
after 24 hours of irradiation showed no 2,3,7,8-TCDD at a detection limit of 0.5
ppm. A bioassay of rabbit ear skin tissue to which the photolysis products had been
applied revealed no chloracnegenic activity.
When a solution of OCDD and isooctane was exposed to artificial sunlight,
about 80 percent of the OCDD remained unreacted after 18 hours. With a solution
of OCDD and 1-octanol, about 94 percent of the OCDD remained unreacted after
20 hours (Stehl et al. 1973).
In a series of tests, thin layers of Herbicide Orange containing 15 ppm 2,3,7,8-
TCDD were exposed to summer sunlight in glass petri dishes (Crosby and Wong
1977). After 6 hours, just over 40 percent of the dioxin remained. A commercial
herbicide composed of butyl esters of 2,4-D and 2,4,5-T and containing 10 ppm
2,3,7,8-TCDD was exposed in the same manner; after 6 hours only about 30
percent of the initial dioxin remained. A commercial mixture containing no
herbicides, but with 10 ppm 2,3,7,8-TCDD was also exposed to sunlight on glass
petri dishes. The original dioxin concentration was reduced by about 90 percent
after 2 hours. Herbicide Orange was applied in droplets to excised rubber plant
leaves and to the surface of Sacramento loam soil; the samples were then exposed
to sunlight. At an application rate of 6.7mg/cm2 of leaf surface, no TCDD's were
detected on the leaves after 6 hours. At a lower application rate of 1.3 mg/cm2,
however, about 30 percent of the TCDD's remained after 6 hours. It was also
reported that upon application to the soil (10 mg/cm2) approximately 90 percent of
the dioxin remained after 6 hours. The authors attributed the lesser degree of
photolysis of 2,3,7,8-TCDD on the soil partly to shading of lower layers by soil
particles.
Investigators in this study concluded that there are three requirements for dioxin
photolysis:
1. Dissolution in a light-transmitting film
2. Presence of an organic hydrogen donor
3. Ultraviolet light
In another study, 2,3,7,8-TCDD deposited on silica gel was irradiated with light
having a wavelength greater than 290 nm. The original concentration of the dioxin
was reduced by 92 percent after 7 days. When irradiation was done with light of
shorter wavelength (>230 nm), the dioxin concentration was reduced by 98
percent after 7 days. It was concluded that cleavage of 2,3,7,8-TCDD was possible
without a proton donor if the intensity of the sun at ground level was great enough
to supply the required irradiation (Gebefuigi, Baumann, and Korte 1977).
239
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In a study reported by Bertoni et al. (1978) about 150 ml/m2 of an ethyloleate-
xylene mixture was sprayed on a 1-cm-deep sample of Seveso soil contaminated
with 2,3,7,8-TCDD. More than 90 percent of the 2,3,7,8-TCDD was destroyed
after 7 days of sunlight exposure. When a dioxin sample was placed in a room
sprayed with ethyloleate-xylene mixture, disappearance of the dioxin was almost
complete after 3 days exposure under a Phillips MLU 300 W lamp. The xylene was
used to reduce viscosity, although ethyloleate was just as effective when used alone.
The more rapid photolysis in the room was attributed mainly to the smooth walls of
the room receiving the full intensity of the radiation, including the wavelength of
light that was absorbed most readily by dioxins.
The smooth gradual decrease of dioxin concentration in the 1-cm-deep soil
samples was unexpected because ultraviolet light does not penetrate soil. It was
hypothesized that dioxin decomposition below the soil surface could result either
from a diffusion mechanism in the oleate medium or from photolytic reactions
occurring through long-lived free radicals.
The solubility and photodecomposition of 2,3,7,8,-TCDD in cationic, anionic,
and nonionic surfactants was studied by use of both pure dioxin samples and
contaminated materials obtained from the Seveso area (Botre, Memoli, and
Alhaique 1979). To test the effectiveness of the solubilizing agents, homogeneous
soil samples were treated twice with surfactant and then three times with the same
volume of water to remove the surfactant. Extracts from the residual soil were then
obtained with benzene and methanol, and the extracts were analyzed for 2,3,7,8-
TCDD. Untreated contaminated soil samples were used for standards. In the pure
dioxin solubilization study, 4 ml of surfactant was used to treat the residues.
Methanol was used as the reference solvent. The surfactants used were sodium
dodecyl sulfate (SDS), and anionic surfactant, 1-hexadecylpyridinium sorbitan
monooleate (Tween 80), hexadecyltrimethylammonium bromide, and 1-
hexadecylpyridinium chloride (CPC).
Results showed that CPC was the best solubilizing agent for contaminated soil
taken from the Seveso area, whereas in the pure dioxin experiment the differences
were slight. Photodecomposition experiments performed using 2,3,7,8-TCDD
dissolved in surfactants and in methanol also revealed CPC as the superior
medium. Irradiation with an ultraviolet lamp for 4 hours destroyed about 90
percent of the dioxin in the CPC solution. Only 50 percent of the dioxin in the SDS
solution was destroyed after 4 hours of irradiation, although almost 100 percent
disappeared after 8 hours. Over 25 percent of the dioxin in methanol remained after
8 hours.
In a small-scale study in Seveso, olive oil was used in either a 40 percent aqueous
emulsion or an 80 percent cyclohexanone solution and applied on a heavily
contaminated area of grassland. These solutions supplied a hydrogen donor in an
effort to facilitate photodegradation of the dioxin present. It was reported that
after 9 days 80 to 90 percent of the 2,3,7,8-TCDD was destroyed, whereas
concentrations in controls remained virtually unchanged (Wipf et al. 1978; Crosby
1978).
In a study of the fate of 2,3,7,8-TCDD in an aquatic environment, samples of
lake sediment and water containing 14C-labeled 2,3,7,8-TCDD were incubated in
glass vials under light and dark conditions for 39 days (Matsumura and Ward
1976). Results indicated no significant photolytic destruction of the dioxin.
Whether artificial or natural light was used is not mentioned.
The fate of 2,3,7,8-TCDD in emulsifiable and granular silvex formulations was
studied after application to microagroecosystems and outdoor field plots (Nash
and Beall 1978). (Experimental conditions of this study are described more
completely in the subsection on physical transport.) It was observed that upon
volatilization, the dioxin in both the emulsifiable and granular formulations was
photolyzed not only in direct sunlight but also in shaded areas outdoors and in
filtered sunlight passing through the glass of the microagroecosystem chambers.
240
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The mean half-life of the dioxin in the emulsifiable concentrate was approximately
7.65 days; the half-life in the granular formulation was 13.5 days. The half-life of
the dioxin in the emulsifiable formulation on grass in a microagroecosystem
ranged from 5 to 7.5 days.
Crosby and Wong reported in 1973 that the major photodecomposition
products of 2,4,5-T are 2,4,5-TCP, 2-hydroxy-4, 5-dichlorophenoxyacetic acid,
4,6-dichlororesorcinol, 4-chlororesorcinol, and 2,5,-dichlorophenol; 2,3,7,8-
TCDD was not detected as a photolysis product.
PHYSICAL TRANSPORT
This section describes studies of the movement of dioxins in or into soil, water,
and air. Because of episodes involving actual contamination, such movement has
become a critical issue. The transport of a chemical in the environment depends
greatly upon the properties of the chemical: Is it soluble in water? Is it volatile?
Does it cling to soils readily? With the answers to these questions, it is possible to at
least postulate reasonably where these chemicals might be found following release
into the environment and by what means human or animal receptors are most
likely to be affected.
Transport in Soil
Many studies have addressed the mobility of dioxins, especially 2,3,7,8-TCDD,
in soils. Generally it has been found that dioxins are more tightly bound to soils
having relatively higher organic content. Dioxins applied to the surface of such
soils generally remain in the upper 6 to 12 inches. They migrate more deeply into
more sandy soils, to depths of 3 feet or more. In areas of heavy rainfall, not only is
vertical migration enhanced but lateral displacement also occurs by soil erosion
with runoff and/ or flooding. Dioxins may appear in normal water leachate from
soils that have received several dioxin applications.
Kearney et al. (1973b) studied the mobility of 2,7-DCDD and 2,3,7,8-TCDD in
five different types of soil. They observed that the mobility of both dioxins
decreased with increasing organic content of the soil. Based on this observation and
the finding that these dioxins were relatively immobile in the soils tested, the
conclusion was that these dioxins would pose no threat to groundwater supplies
because they would not be mobilized deep into soils by rainfall or irrigation.
Similar conclusions were reached by Matsumura and Benezet (1973), who
showed that mobility of 2,3,7,8-TCDD is relatively slow, much slower than that of
DDT. It was concluded that any movement of 2,3,7,8-TCDD in the soil
environment would be by horizontal transfer of soil and dust particles or by
biological transfer (other than by plants).
During the 8-year period from 1962 to 1970, the U.S. Air Force sprayed 170,000
pounds of 2,4-D, and 161,000 pounds of 2,4,5-T, in two herbicide formulations
(Herbicide Orange and Herbicide Purple) over a test area 1 mile square at the Eglin
Air Force Base in Florida (Commoner and Scott 1976). A map of this area is shown
in Figure 64. Originally, the applications were done for the purpose of testing spray
equipment to be used in Vietnam (Young 1974). The exact concentration of
2,3,7,8-TCDD in the herbicides used for the spraying tests is not known but is
estimated to have ranged from 1 to 47 ppm. The test site has since been analyzed for
dioxin residues. In 1970 a 36-in.-deep soil core was taken from a portion of the test
area that had received approximately 947 pounds per acre of the 2,4-D, 2,4,5-T
Herbicide Orange mixture (Woolson and Ensor 1973). At the limits of detection
(0.1 to 0.4 ppb), no 2,3,7,8-TCDD was found at any depth. Several explanations
were presented for the absence of dioxin: 1) the 2,4,5-T applied contained less than
2 ppm of 2,3,7,8-TCDD, a concentration undetectable in the soil by the analytical
method used; 2) the dioxin had migrated to a depth below 36 inches because of the
241
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sandy nature of the soil and the high incidence of rainfall in the area; 3) wind
erosion had displaced the dioxin; and 4) biological and/or photochemical
decomposition had occured.
In 1973, four soil samples were taken from the same test area and analyzed at low
levels for 2,3,7,8-TCDD (Young 1974). The samples contained the dioxin in
approximate concentrations of 10, 11, 30, and 710 ppt, and these concentrations
were confined to the upper 6 in. of the soil layer.
From March, 1974, to February, 1975, the Air Force performed another study at
the Eglin Air Force Base (Bartleson, Harrison, and Morgan 1975). Two test areas
were studied, and also an area where the herbicides had been stored and loaded
onto planes. The original 1-mile-square area sampled in 1971 and 1973 contained
dioxin in concentrations up to 470 ppt. A second test area, designated Grid 1,
contained concentrations of 2,3,7,8-TCDD as high as 1500 ppt. The highest dioxin
concentrations were generally found in low-lying areas, and the lowest
concentrations usually were in areas of loose sand; these findings indicate that the
horizontal translocation had probably occurred through water runoff and wind
and water erosion.
The storage and loading area contained up to 170,000 ppt of 2,3,7,8-TCDD. This
area was elevated relative to a nearby pond. Limited sampling of the pond silt
revealed a maximum concentration of 85 ppt, and 11 ppt was found in the pond
drainage stream. These findings also indicated horizontal translocation of the
dioxin, probably as a result of soil erosion.
A core sample of soil taken from Grid 1 in 1974 showed the following
concentrations of 2,3,7,8-TCDD:
Sample depth, in. Concentration, ppt
0-1 150
1-2 160
2-4 700
4-6 44
These data indicate some vertical movement of 2,3,7,8-TCDD, probably as a result
of water percolation through the soil.
In another test, application of 0.448 kg/m2 of Herbicide Orange to a test site in
Utah resulted in the following concentrations of 2,3,7,8-TCDD 282 days after
application:
Sample depth, in. Concentration, ppt
Control 0-6 <10
0-6 15,000
6-12 3,000
12-18 90
18-24 120
In 1978, additional measurements at the Utah test site were reported (Young et al.
1978). Table 51 presents analytical results of plot sampling 4 years after application
of Herbicide Orange at various rates. Table 52 gives results of a similar test
performed at Eglin Air Force Base in Florida.
In the tests reported in Tables 51 and 52, samples were taken by means of a soil
auger. Subsequent tests revealed that dioxin-containing soil was being carried
downward as a result of the auger sampling technique and that the concentrations
of 2,3,7,8-TCDD below 6 in. were not detectable.
Followup studies of the residual levels of 2,3,7,8-TCDD in three loading areas of
Eglin Air Force Base were conducted during the period from January 1976 to
December 1978 (Harrison, Miller, and Crews 1979). Two of the loading areas were
relatively free of contamination. The third (described above) had surface
243
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TABLE 51. CONCENTRATIONS OF 2,3,7,8-TCDD AT UTAH TEST RANGE
4 YEARS AFTER HERBICIDE ORANGE APPLICATIONS3
(parts per trillion)
Rate of Herbicide Orange application (Ib/acre)
Soil depth (inches) 1000 2000 4000
0-6
6-12
12-18
650
11
NAb
1600
90
NA
6600
200
14
a—Source Young et al. 1978.
b—NA = Not analyzed.
TABLE 52. CONCENTRATIONS OF 2,3,7,8-TCDD AT EGLIN
AIR FORCE BASE 414 DAYS AFTER HERBICIDE ORANGE
APPLICATION3
2,3,7,8-TCDD
Soil depth (inches) Herbicide Orange (ppm) concentration in soil (ppt)
0-6 1866 250
6-12 263 50
12-18 290 <25b
18-24 95 <25b
24-30 160 <25b
30-36 20 <25b
a—Source Young et al 1976
b—Detection limit.
soil concentrations of TCDD's as high as 275 ppb. TCDD's were found at 1 meter
depths at concentrations one-third the surface amount.
The accident at Seveso in July 1976 released quantities of 2,3,7,8-TCDD
estimated to range from 300 g to 130 kg over an area of approximately 250 acres
(Carreri 1978). Because the Seveso soil is drained by an underlying gravel layer,
much concern has arisen over the possibility of groundwater contamination. Early
soil migration studies in some of the most contaminated areas at Seveso showed
that the dioxin penetrated to a depth of lOto 12 in. Later studies reported by Bolton
(1978) found 2,3,7,8-TCDD at soil depths greater than 30 in. An observed 70
percent decrease in 2,3,7,8-TCDD soil concentration over a period of several
months may support the suggestion that the dioxin can be mobilized laterally as
well as vertically from soils during heavy rainfall or flooding (Commoner 1977).
Following the incident at Verona, Missouri, when oil contaminated with 2,3,
7,8-TCDD was sprayed on a horse arena to control dust, the top 12 in. of soil
was removed and replaced with fresh soil. After removal and replacement of the
244
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soil, no further episodes occurred involving sickness or death of human beings or
animals. Investigators concluded that this supported the notion that the vertical
mobility of TCDD's is limited (Commoner and Scott 1976).
Nash and Beall (1978) report studies of the fate of 2,3,7,8-TCDD by use of
microagroecosystems and outdoor field plots. A diagram of the
microagroecosystem is shown in Figure 65. Two commercially available silvex
formulations, one granular and one emulsifiable, were tested. The test and control
formulations were applied three times to turf in five microagroecosystems and once
to turf on the outdoor plots. Throughout the test period a sprinkler system applied
water to the soils to simulate rainfall.
0 ° I Removable Access Panels
Outlet Filter
Holder
Figure 65. Diagram of microagroecosystem chamber.
The 2,3,7,8-TCDD used in the study was labeled with radioactive hydrogen or
3H. Throughout the study the labeled dioxin (or breakdown product) was tracked
by extremely sensitive radiochemical assay methods. The presence of the dioxin
molecule in samples was confirmed by gas-liquid chromatography.
In the first two applications (on days 0 and 35) the concentration of 2,3,
7,8-TCDD in the silvex was 44 ppb. In the third application (on day 77) the
silvex formulations contained 7500 ppb (7.5 ppm) 2,3,7,8-TCDD. Soil, water, air,
grass, and earthworms were analyzed for 2,3,7,8-TCDD at various times following
each of the herbicide applications.
Soil analyses showed that most ( — 80 percent) of the applied 2,3,7,8-TCDD
remained in the top 2 cm of the soil. Trace levels at depths of 8 to 15 cm indicated
some vertical movement of the dioxin in the soil.
Analysis of water leachate samples from the silvex-treated microagroecosystems
following the first two herbicide applications showed no detectable 2,3,7,8-TCDD
(limits of detection were 10~16 gig*). The dioxin was detected later, however,
following the third herbicide application, and maximum concentrations of 0.05 to
0.06 ppb were calculated to possibly be found in the leachate samples taken 7 weeks
after that third application.
*IO "• g/g may also be expressed as 0.1 fg/g (0 I femtogram per gram) It is equivalent to 0.0001 ppt.
245
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In an ongoing study at Rutgers University, 54 soil-core samples (6 in. in depth)
have been taken from samples of turf and sod from areas in the United States
having histories of silvex and/or 2,4-D applications. The EPA will analyze the
samples fordioxins or herbicide residues. Results are not yet available (Hanna and
Goldberg, n.d.).
Transport in Water
Contamination of streams and lakes by 2,3,7,8-TCDD has also been of concern,
especially because of the spraying of 2,4,5-T on forests to control underbrush.
Possible routes of water contamination from spraying are direct
application, drift of the spray, and overland transport after heavy rains. The
latter, however, seldom occurs on forest lands because the infiltration capacity of
forest floors is usually much greater than precipitation rates (Miller, Norris, and
Hawkes 1973).
The transport of dioxin-contaminated soil into lakes or streams by erosion
constitutes another possible route of contamination. This is evidenced by the
detection of 2,3,7,8-TCDD in water samples from a Florida pond adjacent to a
highly contaminated land area (Bartleson, Harrison, and Morgan 1975).
Additionally, several laboratory studies have shown that lakes or rivers could
become contaminated with minute quantities (ppt) of 2,3,7,8-TCDD and possibly
other dioxins through leaching from contaminated sediments. In a study reported
by Isensee and Jones (1975), 2,3,7,8-TCDD was adsorbed to soils, which were then
placed in aquariums filled with water and various aquatic organisms.
Concentrations of the dioxin in the water ranged from 0.05 to 1330 ppt. These
values corresponded to initial concentrations of 2,3,7,8-TCDD in the soil ranging
from 0.001 to 7.45 ppm. The investigators concluded that dioxin adsorbed to soil as
a result of normal application of 2,4,5-T would lead to significant concentrations of
2,3,7,8-TCDD in water only if the dioxin-laden soil was washed into a small pond
or other small body of water.
Other investigations have shown similar results. Using radiolabeled 2,3,7,8-
TCDD, Matsumura and Ward (1976) showed that, after separation from lake-
bottom sediment, water contained 0.3 to 9 percent of the original dioxin
concentration added to the sediment. Results of another test indicated that a total
of about 0.3 percent of the applied dioxin concentration passed through sand with
water eluate (Matsumura and Benezet 1973). In some cases, the observed
concentration of TCDD's in the water was greater than its water solubility (0.2
ppb). The 1976 report suggests that some of the radioactivity apparent in the
aqueous phase was probably due to a combination of lack of dioxin degradation,
presence of 2,3,7,8-TCDD metabolites, and binding or adsorption of TCDD's onto
organic matter or sediment particles suspended in the water.
In another study, application of 14C-TCDD to a silt loam soil at concentrations
of 0.1 ppm led to 14C-TCDD concentrations in the water ranging from 2.4 to 4.2 ppt
over a period of 32 days (Yockim, Isensee, and Jones 1978).
The findings of such investigations are consistent with recent reports that
TCDD's are migrating to nearby water bodies from industrial chlorophenol wastes
buried or stored in various landfills. At Niagara Falls, New York, for example, 1.5
ppb TCDD's have been detected at an onsite lagoon at the Hyde Park dump where
3300 tons of 2,4,5-TCP wastes are buried (Chemical Week 1979a; Wright State
University 1979a,b). Sediment from a creek adjacent to the Hyde Park fill (also in
the Niagara Falls area) is also contaminated with ppb levels of the dioxin
(Chemical Week 1979a, 1979d). In Jacksonville, Arkansas, there is growing
evidence that TCDD's may have migrated from process waste containers in the
landfill of a former 2,4,5-T production site. The dioxins have been found both in a
large pool of surface water on the site (at 500 ppb) and downstream of the facility in
the local sewage treatment plant, in bayou-bottom sediments, and in the flesh of
246
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mussels and fish (Richards 1979; Fadiman 1979; Cincinnati Enquirer 1979;
Tiernan et al. 1980). TCDD's apparently are also being leached into surface and
groundwaters from an 880-acre dump site of the Hooker Chemical Company at
Montague, Michigan (Chemical Week 1979c; Chemical Regulation Reporter
1979b). Dioxins were found at the site at levels approaching 800 ppt.
Transport in Air
One study has been identified in which levels of 2,3,7,8-TCDD in air have been
measured (Nash and Beall 1978). Femtogram (10-'5g) quantities of the dioxin were
detected in the air after granular and emulsifiable silvex formulations containing
radiolabeled 2,3,7,8-TCDD had been applied to microagroecosystems. Air
concentrations of the dioxin decreased appreciably with time following
application. The data appear to confirm that TCDD has a very low vapor pressure
and that loss due to volatilization is extremely low, especially when low levels of
2,3,7,8-TCDD are involved and granular formulations containing the dioxin are
used.
Results of other investigations indicate that water-mediated evaporation of
TCDD's may take place (Matsumura and Ward 1976).
Transport of dioxins by way of airborne particulates has recently received much
attention. Several studies have shown the presence of dioxins in fly ash from
municipal incinerators (Nilsson et al. 1974; Olie, Vermuelen, and Hutzinger 1977;
Buser and Rappe 1978; Dow Chemical Company 1978; Tiernan and Taylor 1980).
A recent report of Dow Chemical Company (1978) contends that particulates from
various combustion sources may contain dioxins and that these dioxin-laden
particulates are a significant source of dioxins in the environment. More details on
these studies are presented in Section 3.
It has also been recently reported that dioxins from buried chlorophenol wastes
are being mobilized by means of airborne dust particles (Chemical Regulation
Reporter 1980a).
BIOLOGICAL TRANSPORT
This section discusses the potential for dioxins to accumulate and to become
concentrated and magnified in biological tissues. In the past, pesticides (most
notably DDT) have been found to accumulate in organisms at almost every trophic
level. In some organisms, these chemicals have been concentrated in the tissues.
When an animal in a higher trophic level feeds on organisms that accumulate these
chemicals, the animal receives several "doses" of the chemical, resulting in what is
termed biomagnification. If this process proceeds to higher levels in the food chain,
the chemicals may become concentrated hundreds or thousands of times, with
possibly disastrous consequences.
The ability for a chemical to accumulate and to become concentrated or
participate in biomagnification depends primarily on its availability to organisms,
its affinity for bioligical tissues, and its resistance to breakdown and degradation in
the organism.
Bioaccumulation, Bioconcentration, and Biomagnification in Animals
The biological activity of dioxins with respect to accumulation, concentration,
and magnification has been addressed by several researchers. Briefly,
bioaccumulation is the uptake and retention of a pollutant by an organism. The
pollutant is said to be bioconcentrated when it has accumulated in biological
segments of the environment. The increase of pollutant concentrations in the
tissues of organisms at successively higher trophic levels is biomagnification.
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Several investigators (Fanelli et al. 1979, 1980; Frigerio 1978) have studied the
levels of TCDD's in animals captured in the dioxin-contaminated area near
Seveso, Italy. Data shown in Table 53 indicate that TCDD's accumulate in
environmentally exposed wildlife. All field mice were found to contain TCDD's at
whole-body concentrations ranging from 0.07 to 49 ppb (mean value 4.5 ppb). The
mice were collected from an area where the soil contamination (upper 7 cm) varied
from 0.01 to 12 ppb (mean value 3.5 ppb). These data are in agreement with Air
Force studies by Young et al. (described below), which indicate that rodents living
on dioxin-contaminated land concentrate TC DD's in their bodies only to the same
order of magnitude as the soil itself; biomagnification does not occur. Several
rabbits and one snake have been found to concentrate TCDD's in the liver. The
snake also had accumulated a very high level of TCDD's in the adipose (fat) tissue.
Liver samples from domestic birds were analyzed for TCDD's with negative
results.
TABLE 53. TCDD LEVELS IN WILDLIFE8
Animal
Field mouse
Hare
Toad
Snake
No. of samples
analyzed Tissue
14
5
1
1
Whole body
Liver
Whole body
Liver
Adipose tissue
TCDD level (ng/g)
(ppb)
Positive
14/14
3/5
1/1
1/1
Average
45
7.7
02
2 7
16.0
Range
0 07-49
2.70-13
Earthworm 2b Whole body 1/2 120
a—Source Fanelli et al 1980
b—Each sample represents a 5-g pool of earthworms
Earlier studies by the Air Force evaluated alternative methods for disposal of an
excess of 2.3 million gallons of Herbicide Orange left from the defoliation program
in Southeast Asia. The studies took place at the test site at Eglin Air Force Base in
Florida (Figure 64) and at test areas in Utah and Kansas.
In June and October of 1973, samples of liver and fat tissue of rats and mice
collected from grids on a 3-mile-square test area (TA C-52A) at Eglin Air Force
Base were analyzed for the presence of TCDD's (Young 1974). The samples
contained concentrations of TCDD's ranging from 210 to 542 ppt. Tissue of
control animals contained less than 20 ppt TCDD's. Because most of the
concentrations of TCDD's in the group of animals tested were higher than those
found in the soil, it was suggested that biomagnification might have occurred;
however, because the animals studied failed to show teratogenic or pathologic
abnormalities, the presence of a substance similar to TCDD's but with a lower
biologic activity was postulated.
Another Air Force report gives results of additional studies conducted at Eglin
Air Force TA C-52A (Young, Thalken, and Ward 1975). In an effort to test the
possible correlation between levels of TCDD's in the livers of beach mice and in
soil, experiments were conducted to determine the possible exposure routes.
Because contamination by TCDD's could be detected only in the top 6 in. of soil, it
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was thought that a food source might be responsible for the presence of the dioxin
in animal tissue. Analysis of seeds (a food source for beach mice) collected in the
area revealed no TCDD's (at 1 ppt detection level); therefore, another route of
contamination was suggested. Since the beach mouse spends as much as 50 percent
of its time grooming, investigators postulated that the soil adhering to the fur of the
mice as they move to and from their burrows was being ingested. As a test of this
hypothesis, a dozen beach mice were dusted 10 times over a 28-day period with
alumina gel containing TCDD's. Analysis of pooled samples of liver tissue from
controls indicated concentrations of TCDD's of less than 8 ppt (detection limit),
whereas concentrations in samples of tissue from the dusted mice reached 125 ppt.
Further analysis was done on samples of liver tissue from beach mice collected
from Grid 1 of TA C-52A. A composite sample of male and female liver tissue
contained TCDD's at levels of 520 ppt, and a composite sample of male tissue
contained 1300 ppt. In contrast, the liver tissue of mice collected from control field
sites contained TCDD's in concentrations ranging from 20 ppt (male and female
composite) to 83 ppt (female composite). Air Force researchers concluded that
although bioaccumulation was evident, there were no data to support
biomagnification because the levels of TCDD's in the liver tissue of beach mice
were in general no greater than levels found in the soil on Grid 1 (rangingfrom <10
to 1500 ppt).
In evaluation of this Air Force study Commoner and Scott (1976) again reached
a different conclusion. Because dioxin concentrations in the pooled liver samples
represented an average value for the mice, they believed that this value should be
compared with average value for TCDD's in the soil of Grid 1, which was 339 ppt.
They concluded that biomagnification was evidenced by the significantly higher
levels of TCDD's in mouse liver than in soil.
Analysis for TCDD's in the six-lined racerunner, a lizard found in the area,
showed concentrations of 360 ppt in a pooled sample of viscera tissue and 370 ppt
in a pooled sample of tissue from the trunks of specimens captured in TA C-52A.
Specimens captured at a control site showed concentrations of TCDD's less than
50 ppt (detection limit).
Early studies of aquatic specimens obtained from ponds and streams associated
with TA C-52A showed no TCDD's at a detection limit of less than 10 ppt (Young
1974). In further studies, however, three fish species showed detectable (ppt) levels
of TCDD's (Young, Thalken, and Ward 1975). Pooled samples of skin, gonads,
muscle, and gut from a species of bluegill, Lepomis puntatus, contained 4, 18, 4,
and 85 ppt TCDD's, respectively. AH of these specimens were obtained from the
Grid 1 pond on TA C-52A, where bluegill was at the top of the food chain. Two
other fish species, Notropis lypselopterus (sailfin shiner) and Gambusia affinis
(mosquito fish), also showed 12 ppt of TCDD's. These specimens were collected
from Trout Creek, a stream draining Grid 1. (Mosquito fish samples consisted of
bodies minus heads, tails, and viscera, whereas shiner samples consisted of gut.)
Inspection of gut contents of Lepomis specimens from Trout Creek showed that
the food source of this fish consisted mostly of terrestrial insects. The source of the
TCDD's was not identified, however.
In another Air Force study, tests were done on 22 biological samples from
TA C52A and 6 samples (all fish) from the pond at the hardstand-7 loading area
designated as HS-7 (Bartleson, Harrison, and Morgan 1975). A composite of
whole bodies of 20 mosquito fish Gambusia collected from the HS-7 pond and 600
feet downstream showed a concentration of 150 ppt TCDD's. Liver samples from
six small sunfish from the HS-7 pond also showed 150 ppt TCDD's, whereas
samples of the livers and fat of 12 medium-sized sunfish from the HS-7 pond
showed concentrations of 0.74 ppb. Because the solubility of 2,3,7,8-TCDD in
water is far below these levels (0.2 ppb), the data seem to indicate biomagnification
in addition to bioaccumulation. The stream that drains the HS-7 pond flows north
into a larger pond known as Beaver Pond. Composite samples of four whole large
249
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fish from Beaver Pond showed a concentration of 14 ppt TCDD's. The livers of 25
large fish and fillets of 8 large fish from Beaver Pond showed no TCDD's at a
detection limit of 5 ppt. A followup study conducted from 1976 to 1978 showed that
TCDD's were present in turtle fat and beach mouse liver and skin (Harrison,
Miller, and Crews 1979).
In the same study, samples obtained from deer, meadowlark, dove, opposum,
rabbit, grasshopper, six-lined racerunner, sparrow, and miscellaneous insects from
TA C-52A were analyzed for TCDD's. TCDD's were detected in the livers and
stomach contents of all of the birds. One composite sample of meadowlark livers
contained 1020 ppt TCDD's, the highest level found in all samples. No TCDD's
were detected in samples from deer, oppossum, or grasshopper. The sample from
miscellaneous insects contained 40 ppt TCDD's, and the composite sample from
racerunners, 430 ppt TCDD. The authors concluded that this study demonstrated
bioaccumulation. The data also indicate that biomagnification may have occurred.
Commoner and Scott (1976b) point out that the average concentration of TCDD's
in soil from TA C-52A was 46 ppt.It should also be noted that the composite insect
sample most likely included insects that are eaten by the birds. In all cases the
concentration of TCDD's in animal liver samples was greater than that in the insect
sample, an indication of the possibility of biomagnification. Because none of the
Air Force studies analyzed for TCDD's in a series of trophic levels,
biomagnification was not clearly demonstrated.
Woolson and Ensor (1972) analyzed tissues from 19 bald eagles collected in
various regions of the country in an effort to determine whether dioxins were
present at the top of a food chain. At a detection limit of 50 ppb, no dioxins were
found.
Another study failed to show dioxin contamination in tissues of Maine fish and
birds (Zitco, Hutzinger, and Choi 1972).
In a similar study 45 herring gull eggs and pooled samples of sea lion blubber and
liver were analyzed for dioxins and various other substances (Bowes et al. 1973).
Analysis by gas chromatography with electron capture and high-resolution mass
spectrophotometry revealed no dioxins.
Fish and crustaceans collected in 1970 from South Vietnam were analyzed for
TCDD's in an effort to determine whether the spraying of Herbicide Orange had
led to accumulation of TCDD's in the environment (Baughman and Meselson
1973). Samples of carp, catfish, river prawn, croaker, and prawn were collected
from interior rivers and along the seacoast of South Vietnam and were immediately
frozen in solid Q>2. Butterfish collected at Cape Cod, Massachusetts, were
analyzed as controls. Samples of fish from the Dong Nai River (catfish and carp)
showed the highest levels of TCDD's, ranging from 320 to 1020 ppt. Samples of
catfish and river prawn from the Saigon River showed levels ranging from 34 to 89
ppt. Samples of croaker and prawn collected along the seacoast showed levels of 14
and 110 ppm of TCDD's, whereas in samples of butterfish from Cape Cod the
mean concentration of TCDD's was under 3 ppt (detection limit). The authors
concluded that TCDD's had possibly accumulated to significant environmental
levels in some food chains in South Vietnam.
Other investigators have studied the accumulation of TCDD's in mountain
beavers after normal application of a butyl ester of 2,4-D and 2,4,5-T to brushfields
in western Oregon (Newton and Snyder 1978). They reported that the home range
of the mountain beavers was small and that among all animals collected inside the
treatment areas the home ranges centered at least 300 feet from the edge of the
treatment area. Thus their food supplies, consisting primarily of sword fern, vine
maple, and salmonberry, had definitely been exposed to the herbicide. Analysis of
11 livers from the beavers showed no TCDD's in 10 of the samples at detection
limits of 3 to 17 ppt. One sample was questionable; the concentration was
calculated at 3 ppt TCDD's.
Investigators in another study analyzed milk from cows that grazed on pasture
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and drank from ponds that had received applications of 2,4,5-T (Getzendaner,
Mahle, and Higgins 1977). Sample collection ranged from 5 days to 48 months
after application; 14 samples were collected within 1 year after application.
Application rates ranged from 1 to 3 pounds per acre. Milk purchased from a
supermarket was used as the control. The control samples contained levels of
TCDD's ranging from nondetectable to 1 ppt. No milk samples from cows grazing
on treated pasture contained levels of TCDD's above 1 ppt.
In a similar study, milk samples were collected throughout the Seveso area just
after the ICMESA accident occurred (Fanelli et al. 1980). The samples were
analyzed for TCDD's by GC-MS methods. Results are given in Table 54. Figure 66
shows the sites where the milk samples were collected. Dioxin levels were highest in
samples from farms close to the ICMESA plant. The high levels of TCDD's found
in the milk samples strongly suggest that human exposure via oral intake must have
occurred after the accident through consumption of dairy products. A milk
monitoring program that has been sampling milk from outside Zone R since 1978
no longer detects TCDD's in any of the samples.
Three research teams have analyzed fat from cattle that had grazed on land
where 2,4,5-T herbicides were applied. In one study, five of eight samples collected
from the Texas A & M University Range Science Department in Mertzon, Texas,
showed the possible presence of TCDD's at low ppt levels when analyzed by gas
chromatography/low-resolution mass spectrometry (Kocher et al. 1978).
TABLE 54. TCDD LEVELS IN MILK SAMPLES COLLECTED NEAR SEVESO
IN JULY-AUGUST 1976a
TCDD concentration (ng/liter)
Map numberb Date of collection (ppt)
1 7/28 76
2 7/28 7919
8/2 5128
8/10 2483
3 7/28 469
8/2 1593
8/10 496
4 8/10 1000
5 7/29 116
6 7/29 59
7 8/3 80
8 8/3 94
9 7/27 180
8/3 75
10 8/5 <40
a—Source. Fanelli et al. 1980.
b—Locations shown in Figure 66.
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ICMESA
IN
Figure 66. Location of farms near Seveso at which cow's milk samples
were collected for TCDD analysis in 1976 (July-August)
Source Fanelli et al 1980
Apparent TCDD concentrations ranged from 4 to 15 ppt at detection limits
ranging from 3 to 6 ppt. In the second study, 11 of 14 samples analyzed contained
TCDD's (Meselson, O'Keefe, and Baughman 1978). The four highest levels
reported were 12, 20, 24, and 70 ppt TCDD. In the third study, Solch et al. (1978,
1980) detected TCDD's in 13 of 102 samples of beef fat at levels ranging from 10 to
54 ppt.
Shadoff and co-workers could find no evidence that TCDD's are
bioconcentrated in the fat of cattle (Shadoff et al. 1977). The animals were fed
ronnel insecticide contaminated with trace amounts of TCDD's for 147 days.
Sample cleanup was extensive to permit low-level detection of the dioxin. Analysis
was by combined gas chromatography/mass spectrometry (both high and low
resolution). No TCDD's were detected at a lower detection limit of 5 to 10 ppt.
Samples of human milk obtained from women living in areas where 2,4,5-T is
used have also been analyzed for dioxins. In one study, four of eight samples were
reported to contain about 1 ppt TCDD's (Meselson, O'Keefe, and Baughman
1978). In a subsequent study, no evidence of 2,3,7,8-TCDD contamination was
found in 103 samples of human milk collected in western states (Chemical
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-------
Regulation Reporter 1980). The lower level of detection in the latter study ranged
from 1 to 4 ppt.
Model ecosystems have been developed in aquariums to study the
bioaccumulation and concentration of several pesticides including TCDD's
(Matsumura and Benezet 1973). Concentration factors for TCDD's calculated
from these studies were:
Daphnia: 2198 Mosquito larvae: 2846
Ostracoda: 107 Northernbrook silverside fish: 54
The authors concluded that the biological and physical characteristics of
organisms played an important role in the bioaccumulation and concentration of
TCDD's and the other pesticides studied. They also indicated that because of the
low solubility of TCDD's in water and liquids and their low partition coefficient in
liquids, TCDD's are not likely to accumulate in biological systems as readily as
DDT.
Another aquatic study involved a recirculating static model ecosystem in which
fish were separated from all the other organisms (algae, snails, daphnia) by a
screened partition (Yockim, Isensee, and Jones 1978). In this study 14C-TCDD was
added to 400 g of Metapeake silt loam clay to yield TCDD's at a concentration of
0.1 ppm. Treated soils were placed in the large chambers of the ecosystem tanks and
flooded with 16 1 of water. One day after the water addition, all organisms except
the catfish were added. Samples of organisms and water were collected on days 1,3,
7, 15, and 32. On day 15 a second group of 15 mosquito fish was added. On day 32
all organisms remaining were collected and counted. Also on day 32, nine channel
catfish were added to the large chambers of the tanks containing the soil. Catfish
were collected 1, 3, 7, and 15 days later. Of the two collected on each day, one was
sacrificed for analysis and one was placed in untreated water.
Bioaccumulation ratios (tissue concentration of TCDD's divided by water
concentration) for the algae ranged from 6 to 2083, the maximum exhibited after 7
days. Bioaccumulation ratios for the snails ranged from 735 to 3731, with the
maximum at 15 days. The ratios in daphnia ranged from 1762 to 7125, with the
maximum at 7 days. The accumulation ratios in the mosquito fish ranged from 676
at day 1 to 4875 after 7 days. All mosquito fish were dead after 15 days, and their
tissues showed an average of 72 ppb TCDD's. No bioaccumulation ratios were
calculated for the catfish, but levels of TCDD's in the tissues ranged from 0.9 ppt
after day 1 to 5.9 ppt after day 15. By day 32 of exposure, all catfish had died. The
average concentration of TCDD's in the tissue at this time was 4.4 ppb.
It was concluded that under normal use of 2,4,5-T, concentration of TCDD's in
sediments of natural water bodies would probably be 104 to 106 times lower than
the concentration used in this experiment, and although the TCDD's could be a
potential environmental hazard, the magnitude of the hazard would depend on
biological availability and persistence in the aquatic ecosystem under conditions of
normal use.
In previously mentioned studies with microagroecosystems, earthworms
contained 0.2 and 0.3 ppt 2,3,7,8-TCDD and/ or breakdown products of TCDD's
following two silvex applications to soil (Nash and Beall 1978). The silvex
contained 44 ppb TCDD's.
Another study not yet completed concerns the possible accumulation of dioxins
in vegetation and earthworms in turf and sod of areas having a history of silvex
and/or 2,4-D applications (Hanna and Goldberg, n.d.).
Isensee and Jones (1975) performed three experiments using algae, duckweed,
snails, mosquito fish, daphnia, channel catfish and other organisms. Radiolabeled
dioxin (I4C-TCDD) was adsorbed to two types of soil, which were then placed in
glass aquariums and covered with water. One day later, daphnia, algae, snails, and
various diatoms, protozoa, and rotifers were added. In one experiment duckweed
plants were also added on the second day. After 30 days, some daphnia were
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analyzed and two mosquito fish were added to each tank. Three days later, all
organisms were harvested; in Experiments II and III, two fingerling channel catfish
were added to each tank and exposed for 6 days. At the conclusion of each
experiment the concentrations of 14C-TCDD in the water and in the organisms
were determined and the concentration factors calculated. Table 55 summarizes
soil application rates in each experiment and type of soil used.
TABLE 55. SOIL APPLICATION RATES AND REPLICATIONS3
Total '"C-TCDD
added per tank
(M9)
149
0
63
63
63
63
0
10
1
0.1
0.01
0
Type of soilb and amount
of '4C-TCDD added
(9)
Experiment 1
L-20
L-20
Experiment II
L-20
L-20 + M-100
L-20 + M-200
L-20 + M-400
L-20
Experiment III
M-100
M-100
M-100
M-100
M-100
Final concentrations
of '"C-TCDD
(ppm)°
7.45
0.00
3 17
0.53
0.29
0.15
0.00
0.10
0.01
0.001
0.0001
0.00
No. of
replicates
3
1
2
2
2
2
2
2
2
2
2
2
a—Isensee and Jones 1975
b—L = Lakeland sandy loam, M = Metapeake silt loam In Experiment II, L was first treated with
14C-TCDD, then dry-mixed with M in treatment tanks.
c—Soil concentrations based on total quantity of soil in tanks
At soil concentrations as low as 0.1 ppb, 14C-TCDD was leached into the water
and accumulated in the organisms. Bioaccumulation factors at this soil
concentration and a water concentration of 0.05 ppt were 2,000 for algae, 4,000 for
duckweed, 24,000 for snails, 48,000 for daphnia, 24,000 for mosquito fish, and
2,000 for catfish, corresponding to concentrations of 0.1,0.2, 1.2, 2.4, and 0.1 ppb
of I4C-TCDD in the tissues. Although some biomagnification was evident, results
were highly variable. The differences in bioaccumulation factors found in this
study relative to those of Yockim et al. (1978) were attributed to system design,
differences in the organisms, and the fact that bioaccumulation factors in the other
study were based on fresh weight whereas those in this study were based on dry
weight.
The authors conclude that since some bioaccumulation ratios were relatively
high (as compared with those observed with other pesticides), especially in daphnia
and mosquito fish, the potential of TCDD's to accumulate in the environment is
considerable. They further project, however, that at suggested application rates of
2,4,5-T, concentrations of TCDD's in the soil would probably not result in
accumulation in biological systems unless erosion or runoff from recently sprayed
areas is discharged to a small body of water (e.g., a pond).
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Dow Chemical Company reported in 1978 on a series of studies to determine
whether dioxins are present in the Tittabawassee River, into which Dow discharges
treated wastes. In one study, rainbow trout were placed in cages at various
locations above and below the Dow Midland plant, in a tertiary effluent stream,
and in clear well water. Five of six fish placed in the tertiary effluent stream showed
levels of TCDD's ranging from 0.2 to 0.05 ppb. Analysis of whole fish exposed for
30 days at a point 6 miles downstream of the effluent discharge showed
concentrations of 0.01 and 0.02 ppb TCDD's. Analysis of whole fish from the
tertiary effluent showed levels ranging from 0.05 to 0.07 ppb.
In a laboratory experiment with 14C-2,3,7,8-TCDD, Dow (1978) determined
that the bioconcentration factor in rainbow trout was about 6600. Dow also
analyzed native catfish taken randomly from various locations in the
Tittabawassee River and tributaries. The analyses showed levels of TCDD's
ranging from 0.07 to 0.23 ppb, levels of OCDD from 0.04 to 0.15 ppb, and one
sample with 0.09 ppb of hexa-CDD. Highest levels of TCDD's and OCDD were
found in fish collected from the Tittabawassee at points approximately 1 to 2 miles
downstream from Dow. Dow noted that caustic digestion used in sample
preparation may have degraded octa-, and hexachlorodioxins. No other fish
analyzed contained detectable levels of TCDD's (Dow Chemical Company 1978).
Subsequent to the Dow studies, the U.S. EPA colleted and analyzed fish samples
from the Tittabawassee, Grand, and Saginaw Rivers in Michigan (Harless 1980).
TCDD's were found in 26 of 35 samples (74 percent) at levels ranging from 4 to 690
ppt. Catfish and carp contained the highest concentrations, while perch and bass
had the lowest. Additional information concerning dioxin in fish from different
sources can be found on pages 175 and 178.
Accumulation in Plants
Because dioxins are sometimes used in herbicides applied on and near areas
where food plants may be growing, it is important to determine whether the dioxins
may be incorporated into the plants. Thus far, few studies have been done to
determine whether dioxins might accumulate in plants. In the few studies that have
considered this question, results seem to indicate that very small amounts
are accumulated in plants.
Kearney et al. (1973a) studied the uptake of DCDD's and TCDD's from soil by
soybeans and oats. Soil applications of 14C-DCDD (0.10 ppm) and I4C-TCDD
(0.06 ppm) were made, and a maximum of 0.15 percent of the dioxins was detected
in the above-ground portion of the oats and soybeans. No dioxins were found in the
grains harvested at maturity. Application of a solution of Tween 80 (a surfactant)
and TCDD's or DCDD's to the leaves of young oat and soybean plants showed no
translocation to other plant parts after 21 days.
Studies of the absorption and transportation of TCDD's by plants in the
contaminated area near Seveso have been reported (Cocucci et al. 1979). Samples
of fruits, new leaves, and, in some cases, twigs and cork were taken from various
types of fruit trees a year after the dioxin contamination occurred. TCDD's were
found in all samples at^g/kg levels. Concentrations in the leaves were 3 to 5 times
higher than in the fruits, which had the lowest concentrtions. Levels in the cork
samples were generally higher than in the leaves, but not as high as in the twigs. The
findings show that the dioxin is translocated from the soil by plants in newly
formed organs and suggest that the lower concentrations in fruits and leaves may
be due to some form of elimination such as transpiration or ultraviolet
photodegradation. The latter possibility would agree with the photolysis results
reported by Crosby and Wong in 1977.
Cocucci and co-workers also examined specimens of garden plants such as the
carrot, potato, onion, and narcissus. Again/ng/kg levels of TCDD's were found. In
all plants, the new aerial portions appeared to contain less dioxin than the
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underground portions. Concentrations of TCDD's differed in the inner and outer
portions of potato tubers and carrot taproots; the variation was attributed to the
prevalence of conductive tissues in these plant parts. The authors again suggested
that the relatively low concentrations in the aerial parts of these garden plants were
due to an elimination process such as transpiration or photodegradation, or
possibly to metabolism of the dioxin by the plants. The elimination hypothesis was
supported by the further observation that when contaminated plants were
transplanted in unpolluted soil, the dioxin content disappeared.
Young et al. (1976) used specially designed growth boxes to study the uptake of
UC-TCDD by Sorghum vulgave plants. After placing Herbicide Orange
containing 14 ppm I4C-TCDD under the soil in the growth boxes, 100 plants were
grown for 64 days. After 64 days the plants were harvested, extracted with hexane,
and analyzed for 14C-TCDD. Some plant samples were also analyzed for
14C-TCDD before hexane extraction by combustion and collection of the COa-
Anaylsis before extraction showed a concentration of about 430 ppt l4C-TCDDin
the plant tissue. After hexane extraction, the concentration of '"C-TCDD in the
plant tissue was reported as being not significantly reduced. Young et al. concluded
that the relatively high I4C activity in the plant tissue could have been due to the
presence of 1) nonhexane-soluble TCDD, 2) a soil biodegradation product of
TCDD's that was taken up, 3) a metabolic breakdown product of TCDD's found
after plant uptake of the TCDD's, or 4) a contaminant in the original 14C-TCDD
stock solution that was taken up by the plant.
As mentioned elsewhere, concentration of 14C-TCDD in algae and duckweed
has been observed. Bioaccumulation factors were 2000 and 4000, respectively
(Isensee and Jones 1975).
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SECTION 8
DISPOSAL AND DECONTAMINATION
GENERAL CONSIDERATIONS
One of the principal unsolved problems that has followed the discovery of
dioxins is development of methods for destroying them once they are produced.
Many investigators have studied various methods for disposing of commercial
chemicals and production wastes that contain these compounds, and further
research is needed. Even more important is the need for methods of destroying
dioxins after they are released into the environment.
Simple out-of-sight storage has been used on several occasions to dispose of
dioxin-contaminated soils and equipment following industrial accidents from the
manufacture of 2,4,5-TCP. Soil contaminated by the application of dioxin-
containing wastes at Verona, Missouri, was used as fill under a new concrete
highway and was also placed in a sanitary landfill. Some was also used as fill at two
residential sites, but was later removed and placed elsewhere (Commoner 1976a).
The soil contaminated by the accident at Seveso, Italy, was partially removed from
moderately contaminated areas and added to the more heavily contaminated areas,
which will remain uninhabitable for an indefinite period of time (Reggiana 1977).
Following an explosion at Coalite and Chemical Products, Ltd., in England,
portions of the plant equipment were buried in an abandoned coal mine (May
1973). Portions of the Phillips Duphar plant in the Netherlands, following its
explosion, were encased in concrete and dumped into the ocean (Hay 1976a).
The quantities of TCDD-containing wastes from the normal manufacture of
2,4,5-TCP that have been buried at various sites in the United States are not well
documented, although some published figures are available. One company at
Verona, Missouri, reportedly disposed of 16,000 gallons of 2,4,5-TCP distillation
residues over an 8-month period (Shea and Lindler 1975). A New York company
reportedly disposed of 3700 tons of 2,4,5-TCP production wastes at three dumps in
the Niagara Falls area over a 45-year period (Chemical Week 1979a). It is estimated
that the 3700 tons of waste produced by this company could contain 100 pounds of
TCDD (Chemical Week 1979a). An Arkansas facility has been producing 2,4,5-
TCP and related products since 1957 and possibly earlier (Sidwell 1976a). Reports
indicate that 3000 barrels of TCP wastes are buried or stored on the manufacturing
site(Fadiman 1979; Cincinnati Enquirer 1979). Many of these barrels were leaking
and contaminating nearby water bodies (Richards 1979a; Tiernan et al. 1980).
There are, at this writing, 3000 barrels now stored in an EPA-approved shelter, and
none are presently leaking. The correction of the drum problem was completed by
Vertac at a cost of about $500,000 (Howard 1980).
Continuation of land disposal is still being proposed as at least a temporary
measure, however. Other proposals include chemical fixation, deep well disposal,
burial in salt mines, and inclusion of these chemicals with nuclear fission by-
products in secured cavities.
Although these practices postpone the need for solving the problems of disposal
and decontamination, they offer no permanent solutions. Techniques that may be
used to decompose dioxins and thereby remove them permanently from the
environment are discussed in this section. The most extensively tested method is
incineration, which entails a high-temperature oxidation of the dioxin molecules.
Physical methods have also been proposed for some applications; these include the
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use of solvents or adsorbents to concentrate dioxins into smaller volumes for final
disposal by incineration or other methods, and also physical methods of
detoxification including exposure to ultraviolet light or gamma radiation.
Proposed chemical techniques include the use of ozone or special chloroiodide
compounds. Biological degradation techniques are also being considered.
INCINERATION DISPOSAL METHODS
Conventional Incineration
Conventional incineration has reached a high level of development for disposal
of pesticides and other highly toxic, hazardous materials (Wilkinson, Kelso, and
Hopkins 1978; Ferguson et al. 1975; Ottinger 1973; Scurlock et al. 1975; U.S. EPA
1977a; U.S. EPA 1975a; Duvall and Rubey 1976). It is often preferred over other
disposal alternatives (Lawless, Ferguson, and Meiners 1975; Kennedy, Stojanovic,
and Shuman 1969), and has been used extensively (Ackerman et al. 1978).
Incineration as defined here does not include open, uncontrolled burning, but
denotes the use of special furnaces equipped with means for accurate regulation of
furnace temperature, supplemental fuel usage, and excess air ratios. Industrial
incinerators are also equipped with some form of emission control, often a water
scrubber. Incinerator off-gas usually contains only low concentrations of carbon
particulates, but does contain chlorine and hydrogen chloride if chlorinated
organic chemicals are being burned.
Incinerator operating conditions currently considered adequate for complete
destruction of 2,3,7,8-TCDD and most other chlorinated organics are a
temperature of at least 1000° C (1932° F) with a dwell time of at least 2 seconds
(Tenzer et al.; Wilkinson et al. 1978). Laboratory tests have demonstrated that
with a dwell time of 21 seconds, only half of the 2,3,7,8-TCDD in a sample
decomposes at 700° C, whereas 99.5 percent decomposes at 800° C (Ton That et al.
1973). This information was apparently generated originally by Dow Chemical
Company and quoted by Dr. Ton That and other authors (Crummett 1980). These
data were obtained with a quartz tube apparutus. Using differential thermal
analysis, two other experimenters have observed that complete destruction occurs
between 800° and 1000° C (Kearney et al. 1973b), which agrees with the work of
Langer et al. (1973). All of these studies have been conducted with relatively pure
samples of dioxins. For incineration of impure mixtures, temperatures above 800°
C are especially important because at lower temperatures (300° to 500°C) more
TCDD may be formed from precursor material (Rappe 1978).
Incineration is now used to dispose of wastes from pesticide manufacture at the
Midland, Michigan, facility of Dow Chemical Company. Stationary and rotary
kiln incinerators used at this location can handle almost any solid, semisolid, or
liquid waste. Dow has emphasized in a 1978 report to the EPA that complete
destruction of dioxins is difficult, in that reducing the concentration of a substance
from 1 ppm to the equivalent of 1 ppb necessitates an overall efficiency of 99.9
percent, which in not possible with conventional high-capacity incinerators.
The most extensive incineration of a waste chemical containing dioxins was the
destruction of 10,400 metric tons (more than 2 million gallons) of Herbicide
Orange left over from military defoliation operations in Southeast Asia (Ackerman
et al. 1978). This substance was decomposed in two large incinerators mounted on
the Vulcanus, a chemical tanker ship operated by a company from the Netherlands.
Burning took place in the mid-Pacific ocean. In three separate trips, the herbicide
was emptied from steel storage drums to railroad tank cars to the cargo holds of the
tanker (the drums were rinsed with diesel fuel, which was added to the herbicide).
The ship was then moved to the burn location, and the mixture was incinerated at
an average flame temperature of 1500° C with an incinerator residence time of 1
second. Flow of combustion air was regulated to maintain a minimum of 3 percent
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oxygen in the stack gases. Combustion efficiency was about 99.9 percent. Stack
effluents were sampled and analyzed routinely, with a minimum detection limit of
0.047 ng/ml (ppb). Only one set of samples contained measurable amounts of
2,3,7,8-TCDD (Tiernan et al. 1979). No analyses were performed for any other
chemical constituents or decomposition products.
This operation also resulted in more than 40,000 steel drums that were still
slightly contaminated with Herbicide Orange. These drums were to have been
crushed mechanically, then shipped to a steel mill to be melted as steel scrap at a
temperature of about 2900° C (Whiteside 1977). No available reports confirm the
completion of this procedure. Portions of the ship used in the incineration
operation were also contaminated with 86 Mg/m2 of Herbicide Orange.
Subsequent decontamination reduced the concentration by as much as 96 percent
(Erk, Taylor, and Tiernan 1979). The decontamination procedure and the fate of
the residue are not known (Chemical Week 1978d).
A high-temperature liquid and solid incinerator is being constructed as a mobile
unit under an EPA contract (Brugger 1978). Its purpose is to decompose hazardous
chemicals such as dioxins, and it is expected to be used to incinerate the dioxin-
contaminated sludge now being stored in Verona, Missouri. It may also be used to
burn some dioxin-contaminated activated carbon remaining from initial efforts by
the U.S. Air Force to remove dioxins from Herbicide Orange by adsorption. This
mobile incineration unit is to be equipped with an afterburner and a scrubber for
the exhaust gases. It will be able to handle the combustion equivalent of 75 gallons
per hour of fuel oils and a solids equivalent of 3.5 tons per hour of dry sand.
In another project, a private partnership plans to convert a tanker for ocean
incineration of toxic wastes including 2,4,5-TCP wastes. The ship will be equipped
with three 25-ton-per-hour incinerators capable of burning a 10,000-ton load of
waste on a week's cruise. The EPA will monitor the test burns during initial
operations (Chemical Week 1979g).
Incineration has been suggested for decontamination of the soil and other
materials at Seveso, Italy (Commoner 1977; Pocchiari 1978), but local political
pressure has killed the idea (Revzin 1979; Chemical Week 1979h). A giant
incinerator was to have been built that would have held each furnace charge at 800°
to 1000° C for 30 to 40 minutes. Estimates of the amounts of soil to be processed
range from 150,000 to 300,000 megagrams. In addition there are huge quantities of
contaminated furniture and decaying plants and small animals (about 87,000 in
number), which are presently quarantined, awaiting final disposal. Authorities
have refused to allow the incinerator to be built because the burning of such
massive amounts of dioxin-contaminated debris would take years. Futhermore,
the residents and authorities fear that the presence of such an incinerator would
result in Seveso becoming the industrial waste dumping ground for all of Italy.
Advanced Incineration Techniques
Two advanced incineration techniques have been studied for the decomposition
of toxic substances. Molten-salt combustion consists of burning a contaminated
chemical with air below the surface of a liquified inorganic material.
Microwave-plasma destruction, although not a true combustion process, converts
a mixture of contaminated chemical and oxygen into elemental oxides through the
action of microwave radiation.
Molten-Salt Combustion—
The technology of molten-salt combustion has been developed over the past 20
years by Atomics International Division of Rockwell International Corporation
(Wilkinson, K'elso, and Hopkins 1978). It has potential application to the
destruction of pesticides and hazardous wastes. A schematic of the process is given
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in Figure 67. A difficulty with developing this system for full-scale practice may be
in locating suitable materials of construction.
The molten salt is sodium or potassium carbonate containing 10 percent by
weight of sodium sulfate. It is maintained at 800° to 1000° C by application of
heating or cooling as needed. When the molten salt is applied to chlorinated
hydrocarbon wastes, the carbon and hydrogen in the waste are oxidized to C02 and
steam, while the chlorine content is changed into sodium chloride. Tests have
demonstrated that this bench-scale combustor can achieve virtually complete
decomposition (more than 99 percent) of chlorinated hydrocarbons, 2,4-D,
chlordane, chloroform, and trichloroethane. The 2,4-D tested was part of an actual
waste that contained 30 to 50 percent 2,4-D and 50 to 70 percent bis-ester and
dichlorophenol tars. The waste was diluted with ethanol and burned at 830° C. This
combustion test destroyed 99.98 percent of the organic materials.
Microwave-Plasma Destruction—
Microwave plasma refers to a partially ionized gas produced by
microwave-induced electron reactions with neutral gas molecules (Bailen and
Hertzler 1976; Bailen 1978). The ionized gas or plasma is derived from the carrier
gas which transports the molecules into the plasma zone (Oberacker and Lees
1977). When oxygen is used as the reactant gas in the plasma, highly reactive
atomic oxygen is produced which then rapidly oxidizes organic compounds
introduced into the system discharge (Bailen 1978).
A laboratory-scale microwave-plasma reactor with capacity of 1 to 5 g/h, and a
pilot-scale reactor with capacity of 430 to 3,200 g/h have been tested by the
Lockheed Palo Alto Research Laboratory under a contract from the EPA (Bailen
and Hertzler 1976). A schematic diagram of these units is shown in Figure 68. Tests
have been conducted with a variety of toxic materials, including two commercial
PCB's, Aroclor 1242, and Aroclor 1254. The laboratory-scale reactor converted
99.9 percent of the PCB's into carbon monoxide, carbon dioxide, water, phosgene,
and chlorine oxides. The pilot-scale reactor converted at least 99 percent of most
materials tested into smaller molecules. One test, however, did not achieve
complete destruction and left a black, tarry substance that still contained PCB's.
The pilot reactor was also used in tests with a commercial clay-supported
formulation of kepone charged to the reactor as compressed solid material, a 10
percent slurry in water, and a 20 percent slurry in methanol. Conversion of at least
99 percent of each charge material to basic oxides and hydrogen chlorine was
achieved in all tests.
Microwave-plasma decomposition has also been used to detoxify U.S. Navy red
dye (Bailen 1978). Specific application of this technique to dioxins is not reported,
although it has been considered for detoxification of dioxin-contaminated wastes
stored in Missouri (Bailen 1977).
PHYSICAL METHODS
Concentration
One approach to disposal or decontamination of toxic substances is by use of
techniques that selectively remove toxic constituents from mixtures. Such
techniques would reduce the volume of material that must be treated and would
offer potential for salvage of useful materials. To date, however, such techniques
have presented serious problems because they have been used to concentrate
dioxins even with no available means or facilities for disposal of the concentrate.
In at least two instances, quantities of activated carbon heavily contaminated
with dioxins are being stored because disposal methods are not available. In this
country, extensive pilot-plant studies of carbon adsorption were conducted before
the Air Force decided to incinerate Herbicide Orange (Whiteside 1977; Young etal.
260
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Stack
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Pesticide
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Figure 68. Schematic of microwave plasma system.
Source: Wilkinson, Kelso, and Hopkins 1978, as adapted from Bailen
and Hertzler 1976.
262
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1978). Although the reprocessing method was technically and environmentally
feasible, it was not possible to demonstrate an acceptable method for safely
disposing of the dioxin-laden carbon. The contaminated carbon is now stored on
an island in the Pacific. Similarly, Union Carbide of Australia created quantities of
dioxin-contaminated carbon in efforts to detoxify 2,4,5-TCP after they became
aware of the 2,3,7,8-TCDD problem in 1969 (Chemical Week 1978b; Dickson
1978). This carbon is still stored in steel drums in that country.
Although data are unavailable, activated carbon apparently can adsorb dioxins
selectively from chemical mixtures, but the carbon cannot be regenerated. Even
after long periods of contact, solvent extraction will not desorb a major portion of
the adsorbate. One study evaluated the desorption of phenol from activated carbon
with 10 different solvents (Modell, deFilippi, and Krukonis 1978). After 2 hours of
continuous extraction, the most effective solvent desorbed only 28 percent of the
phenol. A newly proposed technology for regeneration of activated carbon is the
use of supercritical fluids (fluids in the region of their critical temperatures and
pressures), and in particular supercritical carbon dioxide (Modell, deFilippi, and
Krukonis 1978). With one type of activated carbon (Filtrasorb 300, Calgon Corp.),
100 percent desorption was obtained within 3 hours. After the first regeneration,
however, adsorption capacity of the carbon is only 50 to 85 percent. It is believed
that the initial treatment causes formation of carboxyl, hydroxyl, and carbonyl
groups on the surface of the carbon and that their chemical interation with the
carbon may lead to irreversible adsorption.
In general, carbon adsorption techniques have not been proven effective for
toxics disposal, even if the carbon is to be destroyed by incineration or other
methods. After being contaminated with heavy organic chemicals, activated
carbon must usually be dried and pulverized prior to incineration to ensure
complete destruction. These additional handling steps provide the possibility of
fugitive losses.
Bailen and Littauer (1978) are presently investigating the possibility of using
microwaves to regenerate spent activated carbon. It is not known whether
activated carbon containing dioxins will be evaluated in the study.
Solvent extractions of soil have been shown to be effective in analytical
determinations of TCDD's(Tiernanetal. 1980). It has been suggested that solvents
such as hexane could be used to extract dioxins from soil by use of equipment
similar to that used to extract oil from olive seeds (Commoner 1977). It is not
known whether this concentration process has been tested. The use of steam
distillation has also been suggested as a means of concentrating dioxins, but no
details are available.
Photolysis
The use of light to degrade halogenated aromatic compounds is well established
in published literature (Mitchell 1961; Plimmer 1972, 1978a; Rosen 1971; Watkins
1974; Wilkinson, Kelso, and Hopkins 1978). Regarding degradation of dioxins,
most studies have been concerned with the effect of sunlight on dioxins released
into the environment, as outlined in Section 7. Application of the same principle to
detoxify dioxins with artificial light could lead to a means of decontaminating
chemical mixtures.
The Velsicol Chemical Corporation has proposed such a photolytic system as an
alternative method for disposal of Herbicide Orange (Crosby 1978a, 1978b; Lira
1978). The herbicide mixture would first be hydrolyzed with caustic and converted
into butyl alcohol, water, and salts of 2,4-D and 2,4,5-T. Additional butyl alcohol
would then be used to extract the dioxins. The butyl alcohol and dioxins would be
separated from the phenolic salts and water by decantation, and the organic layer
would be irradiated with ultraviolet light. Irradiation would be accomplished in a
special reaction apparatus, in which thin films of the liquid are exposed to light
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from quartz tubes. Although preliminary tests did succeed in destroying
2,3,7,8-TCDD, the process had not been pursued because the toxicity of the
resulting decomposition products was unknown and the butyl alcohol would have
to be disposed of by incineration or other methods. Further tests of this principle
were discontinued.
No other studies of large-scale decomposition of dioxins by use of artificial light
have been reported. Some laboratory studies have shown that light does not
destroy the structure of dioxins. Under appropriate conditions, light converts the
more toxic dioxins to less toxic forms by removing halogen substituents (Crosby
1971). However, Dow Chemical Company has evidence from ultraviolet spectra of
irradiated solutions containing dioxins of four or less chlorine atoms that the rings
are indeed destroyed (Crummett 1980).
Radiolysis
Radiolysis, an extension of the photolytic method, has been studied
experimentally. Gamma rays having properties similar to light have been shown to
partially degrade dioxins. As with ultraviolet light, these rays may not totally
destroy the dioxin structure, but only remove substituent halogens.
In the most recent series of tests, investigators dissolved 2,3,7,8-TCDD in either
ethanol, acetone, or dioxane at a concentration of 100 ng/ ml (ppb) and irradiated
the solutions at 106 rads/h (Chemical Week 1977; Fanelli et al. 1978). They found
that 97 percent of the dioxin was degraded after 30 hours, when ethanol was the
solvent. Degradation was somewhat slower in the other solvents. All irradiated
samples showed the presence of tri-CDD and DCCD.
In 1976, Buser dissolved OCDD in benzene and hexane at a concentration of 25
g/liter and exposed it to gamma radiation. After 4 hours, 80 percent of the OCDD
was converted into dioxins with five, six, or seven chlorine substituents. Further
degradation did not occur.
Other researchers completed an extended series of tests using gamma radiation
of the ionizing type to destroy pesticides (Craft, K.imbrough, and Brown 1975).
Significant destruction of single representative compounds such as
pentachlorophenol, 2,4,5-T, and 2,4-D was obtained, but no change in PCB's or
mixtures of compounds such as Herbicide Orange could be detected. This test
series led to the conclusion that because of the inefficiency of radiation in
destroying mixtures of pesticides and dioxins, cost would be prohibitive for routine
use of this method in waste treatment.
CHEMICAL METHODS
Several chemical techniques have been proposed for the destruction of toxic
dioxins. Vertac, Inc., reportedly developed a process for safely destroying its
dioxin-containing wastes, but no details are available (Environment Reporter
1979b). Of the five methods outlined in the following paragraphs, only the first two
have been tested specifically with dioxins.
Ozone Treatment (Ozonolysis)
The use of ozone is common in chemical waste treatment applications, especially
in decomposition of cyanides. It has been used most often in laboratory
applications for decomposition of large organic molecules (Wilkinson, Kelso, and
Hopkins 1978).
In a recent test, ozone was bubbled through a suspension of 2,3,7,8-TCDD in
water and carbon tetrachloride. It was reported that after 50 hours, 97 percent of
the 2,3,7,8-TCDD had degraded. In this process, the dioxin apparently is
suspended as an aerosol combined with carbon tetrachloride, which facilitates
ozone attack (Cavolloni and Zecca 1977).
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Another modification of ozone treatment has been developed by Houston
Research, Inc. (Wilkinson, Kelso, and Hopkins 1978; Mauk, Prengle, and Payne
1976). Tests with dioxins, however, have not been reported. In this technique,
treatment with ozone is combined with ultraviolet irradiation. The light activates
organic molecules to a highly energetic state, thereby rendering them more
susceptible to ozone attack. When this technique was applied to
pentachlorophenol and DDT, these compounds were decomposed into carbon
dioxide, water, and hydrochloric acid. A schematic diagram of the apparatus is
shown in Figure 69. Two bench-scale reactors of 10- and 21-liter capacity have been
constructed (Mauk, Prengle, and Payne 1976).
Although these examples indicate that ozone treatment may be effective for use
in dioxin disposal or decontamination, the use of ozone must be combined with
some other mechanism that will activate the dioxin and promote the attack of
ozone.
Chloroiodide Degradation
In a recently described method, 2,3,7,8-TCDD in contaminated soil is degraded
by use of a class of compounds derived from quaternary ammonium salt
surfactants and referred to as chloroiodides (Botre, Memoli, and Alhaique 1979).
The compounds are formulated in micellar solutions with surfactants that increase
the water solubility of the substances. The two derivatives showing the most
degradation potential are alkyldimethylbenzyl-ammonium (benzalkonium)
chloroiodide and 1-hexadecylpyridinium (cetylpyridinium).
When 2,3,7,8-TCDD in benzene was vacuum evaporated and the residue treated
with a cationic surfactant aqueous solution containing benzalkonium
chloroiodide, 71 percent of the 2,3,7,8-TCDD decomposed. When cetylpyridinium
chloroiodide in cetylpyridinium chloride was used, 92 percent of the 2,3,7,8-TCDD
was decomposed. These experiments were performed in absence of light to prevent
photolytic degradation.
In a test with soil from Seveso contaminated with 2,3,7,8-TCDD, only about 14
percent was degraded within 24 hours following treatment with benzalkonium
chloride. When benzalkonium chloroiodide was added, an additional 38 percent of
the 2,3,7,8-TCDD was degraded. Total degradation during this test was 52 percent.
Wet-Air Oxidation
Wet-air oxidation is an accelerated oxidation process performed at high pressure
and temperature. Oxidation takes place in an autoclave in which a charge of water
and organic material is heated to 150° to 350° C while being pressurized with air to
40 to 140 atmospheres. Three commercial processes of this type are known as the
Zimpro, Wetox, and Lockheed processes. They are used for rapid decomposition
of sewage sludge, munitions waste, and sulfite liquor from pulp and paper mills. It
has been proposed to evaluate the Wetox system for disposal of priority pollutants
and other hazardous chemicals (Wertzman n.d.). This might also be an alternative
method for disposal of dioxin and dioxin-contaminated materials, but no tests
have yet been reported.
Chlorinolysis and Chlorolysis
Although chlorinolysis and chlorolysis were developed primarily to produce
chlorinated products from nonchlorinated or less-chlorinated organics, some
attention has been focused on their use in waste treatment (Shiver 1976).
Chlorinolysis is used primarily to convert hydrocarbons containing one to three
carbon atoms into perchloroethylene, trichloroethylene, and carbon tetrachloride
(Diamond Alkali Company 1950; U.S. Patent Office 1972). As most often
practiced, the process continuously reacts chlorine with ethylene or ethylene
265
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Figure 69. Schematic for ozonation/ultraviolet irradiation apparatus.
Source: Wilkinson, Kelso, and Hopkins 1978, as adapted from Mauk, Prengle,
and Payne 1976.
266
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dichloride in a fluid bed catalyst reactor. The process usually creates small amounts
of hexachlorobenzene, hexachloroethane, hexachlorobutadiene,
tetrachloroethane, and pentachloroethane as side-reaction products.
Chlorolysis, an associated process, is sometimes used to convert the side-
reaction products from chlorinolysis into carbon tetrachloride; it can also be used
with benzene or its derivatives or with mixtures of chlorinated aromatic or
aliphatic compounds. Chlorolysis is a two-stage process in which gaseous feed
materials are reacted with chlorine at pressures of 200 to 700 atmospheres and
temperatures up to 800°C. No catalyst is used.
In cooperation with the U.S. Department of Agriculture, the Diamond
Shamrock Corporation conducted pilot-plant studies to test the stability of 2,3,7,8-
TCDD under the severe reaction conditions of Chlorolysis (Kearney et al. 1973).
Although the results of these studies are not known, the techniques may be
applicable to disposal of certain dioxin-contaminated chemicals and might yield
marketable products from otherwise waste chemicals.
Catalytic Dechlorination
Catalytic dechlorination is a simple chemical process in which the action of a
catalyst reductively dechlorinates an organic compound. The usual catalyst is
nickel borohydride, which is prepared in a reaction vessel by mixing sodium
borohydride and nickel chloride in a solvent of alcohol. When this solution is
mixed with a chlorinated organic chemical, the chlorine atoms are removed from
the molecules and hydrogen atoms are substituted (Cooper and Dennis 1978;
Dennis 1972; Dennis and Cooper 1975, 1976, 1977; Wilkinson, Kelso, and Hopkins
1978).
Laboratory tests have been conducted with this process to detoxify several
commercial pesticides, including DDT's, heptachlor, chlordane, and lindane. Tests
with chlorinated dioxins have not been reported. The process does not completely
dechlorinate most organic chemicals and would not break down the basic dioxin
structure. The reaction occurs rapidly, however, and at room temperature; for
these reasons, the process may be of value in decontamination operations or in
detoxifying small volumes of toxic dioxins.
Other processes have been used to dechlorinate aromatic compounds, including
conventional catalytic hydrogenation with metallic catalysts and hydrogen gas
(Dennis and Cooper 1975). In a small-scale laboratory experiment with a catalyst
of palladium on charcoal, about 60 percent of a charge of 1,6-DCDD was reduced
to unsubstituted dioxin in 1 hour at room temperature and less than 1 atmosphere
pressure.
BIOLOGICAL TREATMENT
One of the least expensive techniques for breaking down large organic
molecules, and often one of the most effective, is to subject the molecules to the
action of microorganisms. Although toxic chemicals are usually degraded slowly in
uncontrolled exposure to the environment, more complete and more rapid
breakdown can be achieved by controlling the microorganism species and
providing specialized environments.
Numerous studies have examined the susceptibility of dioxins, particularly
2,3,7,8-TCDD, to microbial decomposition. Most of the studies have concerned
decomposition in the uncontrolled environment, as described in Section 6. Much
less attention has been directed to the controlled use of microorganisms. The
following paragraphs describe available data on two aspects of the microbial
decomposition of dioxins: soil conditioning and biochemical wastewater
treatment. A specialized treatment system for toxic wastes is also discussed.
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Soil Conditioning
The large area of dioxin-contaminated soil surrounding Seveso, Italy, has
stimulated studies of degradation of dioxins by soil microorganisms. Available
data indicate that 2,3,7,8-TCDD is resistant to this method of decontamination,
although under optimum conditions some slow degradation occurs.
Rates of uncontrolled degradation have been variously measured in two studies.
The U.S. Air Force reported the half-life of 2,3,7,8-TCDD at 225 and 275 days
(Young et al. 1976). In a separate analysis of the same test data, Commoner(1976b)
obtained a half-life of 190 to 330 days. In Seveso, however, Bolton( 1978) reported
finding no reduction in dioxin levels in the most heavily contaminated zone, and in
the less contaminated zone reduction after 400 days was only 25 percent.
Researchers in Zurich, Switzerland, have found that soil-bound 2,3,7,8-TCDD
becomes increasingly difficult to recover quantitatively with time (Huetter 1980).
This observation may explain the decreasing recoveries of 2,3,7,8-TCDD in soil
degradation studies by the U.S. Air Force and others in which the "disappearance"
of 2,3,7,8-TCDD with time was interpreted as evidence of biodegradation.
Half-lives for 2,3,7,8-TCDD calculated from these studies may not accurately
reflect the true persistance of this dioxin in the soil environment.
One proposal for modifying the Seveso soil environment is to use charcoal or
activated carbon to hold the dioxins in the soil, then to spread manure on the
treated soil to increase the rate of bacterial growth (Young 1976). U.S. Air Force
studies have shown, however, that although treatment of this sort increases the
number and activity of soil microorganisms, the rate of dioxin degradation is
reduced. Apparently, adsorption on charcoal causes the dioxin to be less available
to the bacteria. No other proposals to modify the open soil environment have been
advanced.
Attempts have been made to inoculate Seveso soil with selected bacteria that
might facilitate the breakdown of dioxins. Although initial results appeared
promising, subsequent data indicated that the method had not been effective
(Commoner 1977). The inoculated species either died out or mutated to a strain
that rejected dioxins. In a similar laboratory study of 100 microbial strains that had
shown ability to degrade pesticides, only 5 showed any ability to degrade 2,3,7,8-
TCDD (Matsumura and Benezet 1973).
Wastewater Treatment Systems
Very little is known concerning the ability of biological or biological/chemical
wastewater treatment to remove dioxins.
Dow Chemical Company operates a tertiary treatment system to treat
wastewater from its Midland, Michigan, pesticide manufacturing plant (Dow
Chemical Company 1978). A two-year program of analysis of grab and composite
samples taken from the tertiary effluent stream revealed only one with a detectable
amount (0.008 ppb) of TCDD's. In further investigations, six caged fish were
placed in the tertiary pond effluent; subsequent analyses showed, in five of the six
fish, concentrations of TCDD's ranging from 0.02 to 0.05 ppb in the edible portions
and from 0.05 to 0.07 ppb in the whole bodies. These findings, when compared with
data on control fish containing no detectable levels of TCDD's, clearly indicate the
presence of TCDD's in the tertiary pond effluent.
Data obtained in 1976 from Transvaal, Inc., showed no TCDD's in effluent from
the city stabilization ponds, to which Transvaal sends all or part of its plant
wastewater effluent (Sidwell 1976b). A sample from the Transvaal plant effluent,
however, showed 0.2 to 0.6 ppb of this dioxin. Other than pH adjustment with lime,
the effluent apparently undergoes no pretreatment. As previously discussed (p. 173)
more recent studies of this site have been reported (Tiernan et al. 1980).
In a third study, sludge was sampled at the outlet of a lagoon holding effluent
from a pentachlorophenol manufacturing plant. The sludge was analyzed for
268
-------
TCDD's, but none was found (U.S. Environmental Protection Agency 1978d).
Since this dioxin has never been found as a decomposition product of
pentachlorophenol, the negative analysis would be expected. The sludge was not
analyzed for hexa-CDD's, hepta-CDD's, or OCDD, the dioxins normally
associated with PCP manufacture.
Researchers in Finland have patented a process for purifying wastewaters
containing chlorinated aromatics in a biofilter (Salkinoja-Salonen 1979a). The
filter consists of a layer of wood bark that contains a strain of bacteria able to
degrade the organic compounds (Salkinoja-Salonen 1979 a,b). These bacterial
strains were isolated by taking samples of bacteriferous water, mud, or bark residue
from water bodies polluted by chlorinated and unchlorinated phenols and
aromatic carboxylic acids, then feeding pollutants to the bacterial populations
collected. Work is under way to prove the effectiveness of the filter in treating
dioxins; its efficacy in treating aromatics such as tri- and tetrachlorophenols has
been demonstrated.
Micropit Disposal
A detailed study of biological degradation of pesticides is being conducted by
Iowa State University (Rogers and Allen 1978). The apparatus used in the study,
shown in Figure 70, consists of a partially buried polyethylene garbage can filled
with layers of rock and soil, and flooded with water. The study, sponsored by the
U. S. E PA, deals with a variety of pesticides at various concentrations, and with the
effects of nutrient additives and aeration. Two organochloride compounds are
included among the pesticides being examined, but it is not clear whether the test
includes dioxins. Test data are not available.
269
-------
Ground Level
Galvanized
Basket
Rock
Galvanized
Metal Sleeve
212 Liter
Polyethylene
Barrel
Perforated
Clay Tile
55.2 cm
(1.8ft)
Figure 70. Internal view of pesticide micropit.
Source Rogers and Allen 1978.
270
-------
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301
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306
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APPENDIX A
The tables that follow list organic chemicals and pesticides selected for study on
the basis of potential dioxin contamination, with known producers and production
locations, present and past. The primary source of producer information is the
Stanford Research Institute Directory of Chemical Producers. The tabulations are
by chemical, with producers and locations; and by producer and location, with
chemicals. The tabulations by chemical (Tables Al, A2, A3, and A6) are segregated
according to the classifications based on dioxin concern as defined in Section 3.
The classification information is also noted in the producer location tables by
means of Roman numerals following the chemical names.
The tabulations by producer and location (Tables A4 and A7) group all of the
critical chemicals involved at each manufacturer location. These lists do not
necessarily define the site subject to exposure, because many dumps are remote
from the plants; they do provide a starting point for such definition. Abandoned
production of a chemical or abandoned facilities may present special problems.
Therefore, the production facilities noted since 1968 but no longer active in 1978
are footnoted and are also extracted in separate tables (Tables A5 and A8). Some of
these sites remain active in other production, and some may retain production
capability and/or minor production of the subject chemical. Other plant sites may
be totally deactivated or abandoned. The producer listed is the last known
operator.
Some of the company names of producers designate subsidiary or divisional
names, with notation of the parent company. Company addresses, from the
Stanford Research Institute Directory and from the Thomas Register, are for the
last known producer at a given location and are subject to the uncertainties
introduced by acquisitions and name changes.
307
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TABLE A1. PRODUCERS OF CLASS I ORGANIC CHEMICALS
Chemical
Producer
Location
4-Bromo-2,5-dichlorophenol
2-Chloro-4-fluorophenol
Decabromophenoxybenzene
2,4-Dibromophenol
2,3-Dichlorophenol
2,4-Dichlorophenol
2,5-Dichlorophenol
2,6-Dichlorophenol
3,4-Dichlorophenol
Pentabromophenol
2,4,6-Tnbromophenol
Velsicol
Olin
Great Lakes Chem
Dow
White Chem.
Specialty Organics
Aldrich
Diamond Shamrock
Dow
Monsanto
Rhodia
Transvaal
Velsicol
Aldrich
Specialty Organics
Aldrich
Michigan Chem.
R.S.A.
White Chem.
Dow
Eastern Chem
Guardian
Velsicol
R.S A.
White Chem.
Beaumont, TX
Rochester, NY
El Dorado, AR
Midland, Ml
Bayonne, NJ
Irwindale, CA
Milwaukee, Wl*
Newark, NJ*
Midland, Ml
Sauget, IL
Freeport, TX
Jacksonville, AR
Beaumont, TX
Milwaukee, Wl
Irwindale, CA
Milwaukee, Wl
St Louis, Ml*
Ardsley, NY*
Bayonne, NJ
Midland, Ml*
Pequannock, NJ*
Hauppauge, NJ
Pequannock, NJ*
St. Louis, Ml*
Ardsley, NY*
Bayonne, NJ
*No longer produced at this location
308
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TABLE A2. PRODUCERS OF CLASS II ORGANIC CHEMICALS
Chemical
Producer
Location
Bromophenetole
o-Bromophenol
2-Chloro-1,4-diethyoxy-5-
nitrobenzene
5-Chloro-2,4-dimethoxyaniline
Chlorohydroquinone
o-Chlorophenol
2-Chloro-4-phenylphenol
4-Chlororesorcinot
2,6-Dibromo-4-nitrophenol
3,5-Dichlorosalicylic acid
2,6-Diiodo-4-nitrophenol
3,5-Dnodosalicylic acid
o-Fluoroanisole
o-Fluorophenol
Tetrabromobisphenol-A
Tetrachlorobisphenol-A
R.S.A.
Eastman Kodak
R.S.A.
Fairmount Chem.
GAP
Pfister
GAP
Pfister
Eastman Kodak
Eastern Chem.
Guardian
Dow
Monsanto
Dow
Am. Color & Chem.
GAP
Martin Marietta
Maumee
Sherwin Williams
Aceto
Inmont Corp.
R.S A.
Morton Chem.
RS.A.
Olin
Olin
Dow
Great Lakes
Velsicol
Dover
Ardsley, NY
Rochester, NY
Ardsley, NY
Newark, NJ
Rensselaer, NY
Newark, NJ*
Rensselaer, NY
Ridgefield, NJ
Newark, NJ*
Rochester, NY
Pequannock, NJ*
Hauppauge, NY*
Pequannock, NJ*
Midland, Ml
Sauget, IL
Midland, Ml
Lock Haven, PA
Rensselaer, NY
Sodyeco, NC*
St. Bernard, OH*
St. Bernard, OH*
Carlstadt, NJ
Carlstadt, NJ*
Ardsley, NY
Ringwood, IL*
Ardsley, NY*
Rochester, NY
Rochester, NY
Midland, Ml
El Dorado, AR
St. Louis, Ml
Dover, OH*
*No longer produced at this location
309
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TABLE A3. PRODUCERS OF CLASS III ORGANIC CHEMICALS
Chemical
3-Amino-5-chloro-2-
hydroxybenzenesulfonic acid
2-Amino-4-chloro-6-nitrophenol
o-Anisidine
Benzaldehyde
Bromobenzene
o-Bromofluorobenzene
o-Chlorofluorobenzene
3-Chloro-4-fluoronitrobenzene
3-Chloro-4-fluorophenol
4-Chloro-2-nitrophenol
Chloropentafluorobenzene
2,4-Dibromofluorobenzene
3,4-Dichloroanilme
Producer
Allied
Nyanza
Toms River Chem.
Nyanza
Am. Color and Chem.
Am. Aniline
du Pont
Monsanto
Crompton and Knowles
Dow
Fritzsche
Kalama Chem.
Monroe Chem.
F. Ritter
Stauffer
Tenneco
UOP
Velsicol
Dow
Velsicol
Olin
Olm
Olin
Olm
du Pont
Maumee
Sherwm Williams
Whittaker
Olin
Blue Spruce
Chem. Insecticide
du Pont
Martin Marietta
Monsanto
Location
Buffalo, NY*
Ashland, MA
Toms River, NJ
Ashland, MA
Lock Haven, PA
Lock Haven, PA*
Deepwater, NJ
St Louis, MO*
Fair Lawn, NJ
Kalama, WA*
Clifton, NJ*
Kalama, WA
Eddystone, PA
Los Angeles, CA*
Edison, NJ*
Nixon, NJ*
Fords, NJ*
Garfield, NJ
East Rutherford, NJ
Chattanooga, TN*
Midland, Ml
St. Louis, Ml*
Rochester, NY
Rochester, NY
Rochester, NY
Rochester, NY
Deepwater, NJ*
St. Bernard, OH*
St. Bernard, OH*
San Diego, CA*
Rochester, NY
Bound Brook, NJ
Edison, NJ*
Metuchen, NJ*
Deepwater, NJ
Sodyeco, NC*
Luling, LA
Sauget, IL*
(continued)
310
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TABLE A3. (continued)
Chemical
Producer
Location
o-Dichlorobenzene
3,4-Dichlorobenzaldehyde
3,4-Dichlorobenzotrichloride
3,4-Dichlorobenzotnfluoride
1,2-Dichloro-4-nitrobenzene
3,4-Dichlorophenyhsocyanate
3,4-Difluoroaniline
o-Difluorobenzene
1,2-Dihydroxybenzene-3,5-
disulfonic acid, disodium salt
2,5-Dihydroxybenzenesulfonic
acid
2,5-Dihydroxybenzenesulfonic,
acid, potassium salt
2,4-Dinitrophenol
Allied
Chem. Products
Dover
Dow
du Pont
Hooker
Monsanto
Montrose Chem.
Neville Chem.
Olin
PPG
Solvent Chem.
Specialty Organics
Standard Chlorine
Tenneco
Tenneco
Tenneco
Blue Spruce
Chem Insecticide
Martin Marietta
Monsanto
Plastifax
Mobay Chem.
Ott Chem.
Olin
Olin
Sterling Drug
Eastman Kodak
Nease Chem.
Nease Chem.
Martin Marietta
Mobay
Syracuse, NY*
Cartersville, GA*
Dover, OH*
Midland, Ml
Deepwater, NJ*
Niagara Falls, NY*
Sauget, IL
Henderson, NV
Santa Fe Springs, CA*
Mclntosh, AL*
Natrium, WV
Niagara Falls, NY
Maiden, MA*
Irwindale, CA
Delaware City, DE
Kearny, NJ
Fords, NJ
Fords, NJ
Fords, NJ*
Bound Brook, NJ
Edison, NJ*
Metuchen, NJ*
Sodyeco, NC*
Sauget, IL*
Gulf port, MS
New Martinsville, SC
Muskegon, Ml*
Rochester, NY
Rochester, NY
New York, NY*
Rochester, NY*
State College, PA*
State College, PA*
Sodyeco, NC
Bushy Park, SC
2,4-Dimtrophenoxyethanol
(continued)
Hummel Chem.
Newark, NJ*
South Plainfield, NJ
311
-------
TABLE A3. (continued)
Chemical
3,5-Dimtrosalicylic acid
Fumaric acid
Hexabromobenzene
Hexachlorobenzene
Hexafluorobenzene
Maleic acid
Maleic anhydride
o-Nitroanisole
Producer
Eastman Kodak
Hummel Chem.
Salsbury Labs
Allied
Alberta Gas
Hooker
Monsanto**
Petro-Tex
Pfizer
Reichold
Stepan Chem
Tenneco
U.S Steel
Velsicol
Dover
Hummel Chem.
Stauffer
PCR
Whittaker
Allied
Eastman Kodak
Pfanstiehl Labs
Allied
Amoco
Asland
Chevron
Koppers
Petro-Tex
Monsanto
Reichhold
Standard Oil of Indiana
(see Amoco above)
Tenneco
U S. Steel
du Pont
Monsanto
Location
Rochester, NY
Newark, NJ*
South Plamfield, NJ*
Charles City, IA
Buffalo, NY*
Moundsville, WV*
Duluth, MN
Arecibo, PR
St. Louis, MO
Houston, TX*
Terre Haute, IN
Morns, IL*
Fieldsboro, NJ*
Garfield, NJ
Neville Island, PA
St Louis, Ml
Dover, OH*
Newark, NJ*
South Plamfield, NJ*
Louisville, KY*
Gainesville, FL
San Diego, CA*
Louisville, KY*
Buffalo, NY*
Marcus Hook, PA
Moundsville, WV*
Rochester, NY*
Waukegan, tL
Moundsville, WV*
Johet, IL
Neal, WV
Richmond, CA*
Bridgeville, PA
Cicero, IL
Houston, TX*
St. Louis, MO
Elizabeth, NJ
Morris, IL
Fords, NJ
Neville Island, PA
Deepwater, NJ
Sauget, IL*
St. Louis, MO
(continued)
312
-------
TABLE A3. (continued)
Chemical
Producer
Location
2-Nitro-p-cresol
o-Nitrophenol
Pentabromochlorocyclohexane
Pentabromoethylebenzene
Pentabromotoluene
Pentachloroaniline
Pentafluoroaniline
o-Phenetidine
Phenol (from chlorobenzene)
Sherwin Williams
du Pont
Monsanto
du Pont
Dow
Hexcel
White Chem.
Olm
Whittaker
Am. Aniline
Monsanto
Dow
Hooker
Chicago, IL
Deepwater, NJ*
Sauget, IL
Deepwater, NJ
Midland, Ml
Sayreville, NJ
Bayonne, NJ
Rochester, NY
San Diego, CA*
Lock Haven, PA*
St. Louis, MO*
Midland, Ml*
North Tonawanda, NY*
1-Phenol-2-sulfunc acid,
formaldehyde condensate
Phenyl ether
Phthalic anhydride
Union Carbide
Allied
Diamond Shamrock
Rohm and Haas
Dow
Fritzsche
Monsanto
Allied
BASF Wyandotte
Chevron
Commonwealth Oil
Conoco
Exxon
W. R. Grace
Hooker
Koppers
Monsanto
South Shore, KY*
Marietta, OH*
Buffalo, NY
Cedartown, GA*
Philadelphia, PA
Midland, Ml
Clifton, NJ*
Chocolate Bayou, TX
Buffalo, NY*
Chicago, IL*
El Segundo, CA
Frankford, PA*
Ironton, OH*
Kearny, NJ
Perth Amboy, NJ*
Richmond, CA
Penuelas, PR*
Hebronville, MA*
Baton Rouge, LA
Fords, NJ*
Arecibo, PR
Bridgeville, PA
Chicago, IL*
Cicero, IL
Bridgeport, NJ
Chocolate Bayou, TX*
St. Louis, MO*
Texas City, TX
(continued)
313
-------
TABLE A3. (continued)
Chemical
Producer
Location
Phthalic anhydride
(continued)
Picric acid
Sodium picrate
Tetrabromophthalic anhydride
1,2,4,5-Tetrachlorobenzene
Tetrachlorophthalic anhydride
Tetrafluoro-m-phenylenediamme
Tnbromobenzene
1,2,4-Trichlorobenzene
2,4,6-Trinitroresorcinol
Reichhold
Sherwin Williams
Stand. Oil Co. Cal.
(see Chevron)
Stepan Chem
Union Carbide
U.S. Steel
Witco Chem.
Allied
du Pont
Hummel Chem.
Martin Marietta
Hummel Chem.
Martin Marietta
Northrop
Velsicol
Dover
Dow
Hooker
Solvent Chem.
Standard Chlorine
Hooker
Monsanto**
Whittaker
Velsicol
Northrop
Chris Craft
Dover
Dow
Hooker
Neville Chem.
Sobin Chems.
Solvent Chem.
Standard Chlorine
Sun Chem.
Northrop
Olm
Azusa, CA*
Elizabeth, NJ*
Morris, IL*
Chicago, IL*
Elwood, IL
Millsdale, IL*
Institute, WV*
South Charleston, SC*
Neville Island, PA
Chicago, IL*
Perth Amboy, NJ*
Buffalo, NY*
Deepwater, NJ*
South Plainfield, NJ*
Sodyeco, NC
South Plainfield, NJ
Sodyeco, NC*
Asheville, NC
St. Louis, Ml
Dover, OH*
Midland, Ml
Niagara Falls, NY*
Maiden, MA*
Delaware City, DE
Niagara Falls, NY
Bridgeport, NJ
San Diego, CA*
St. Louis, Ml*
Asheville, NC
Newark, NJ*
Dover, OH*
Midland, Ml
Niagara Falls, NY*
Santa Fe Springs, CA*
Newark, NJ*
Maiden, MA*
Delaware City, DE
Kearny, NJ*
Chester, SC*
Asheville, NC
East Alton, IL
*No longer produced at this location
**Possibly two plants
314
-------
TABLE A4. ALPHABETICAL LIST OF ORGANIC CHEMICAL PRODUCERS
Producer
Location
Chemical (class)
Aceto Chem Co., Inc.
126-02 Northern Blvd.
Flushing, NY 11368
Arsynco, Inc. Subsid.
Alberta Gas Chems., Inc.
Address not available
Aldrich Chem. Co., Inc.
940 West St. Paul Av.
Milwaukee, Wl 53233
Allied Chem Corp.
Columbian Rd. and Park Av
Morristown, NJ 07960
Carlstadt, NJ
Duluth, MN
Milwaukee, Wl
Buffalo, NY
Chicago, IL
El Segundo, CA
Frankford, PA
Ironton, OH
Marcus Hook, PA
Moundsville, WV
American Aniline
Products, Inc
25 McLean Blvd.
P.O. Box 3063
Paterson, NJ 07509
Owned by Pepsi, Inc 52%
and Kopper Co., Inc., 48%
American Color and Chem.
Corp
11400 Westinghouse Blvd.
P.O Box 1688
Charlotte, NC 28201
Amoco Chems. Corp.
200 E. Randolph Dr.
Chicago, IL 60601
Affiliate of Standard Oil Co.,
Indiana
(continued)
Syracuse, NY
Lock Haven, PA
Lock Haven, PA
Joliet, IL
3,5-Dichlorosalicylic acid (II)
Fumaric acid (III)
2,4-Dichlorophenol (I)*
2,6-Dichlorophenol (I)
3,4-Dichlorophenol
3-Ammo-5-chloro-2-
hydroxybenzenesulfonic
acid (III)*
Fumaric acid (III)*
Maleic acid (III)*
1-Phenol-2-sulfonic acid,
formaldehyde condensate
(III)*
Phthalic anhydride (III)*
Picric acid (III)*
Phthalic anhydride (III)*
Phthalic anhydride (III)
Phthalic anhydride (III)*
Phthalic anhydride (III)*
Maleic acid (III)
Fumaric acid (III)*
Maleic acid (III)*
Maleic anhydride (III)*
o-Dichlorobenzene (III)*
o-Anisidine (III)*
o-Amsidine (III)
4-Chlororesorcinol (II)
Maleic anhydride (III)
315
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Arsynco
Ashland Oil, Inc.
See Aceto
Neal, WV
Maleic anhydride (III)
1409 Winchester Av.
P.O. Box 391
Ashland, KY41101
BASF Wyandotte Corp.
100 Cherry Hill Road
Pansppany, NJ 07054
Blue Spruce Co.
1390 Valley Road
Stirling, NJ 07980
Chemical Insecticide Corp.
30 Whitman Av.
Metuchen, NJ 08840
No current address
Chemical Products Corp.
48 Atlanta Road
Cartersville, GA 30120
Chevron Chem. Co.
575 Market Street
San Francisco, CA 94105
Subsid. Standard Oil Co
of California
Chris Craft Industry, Inc
600 Madison Av
New York, NY
See Montrose Chem.
Commonwealth Oil Refining Penuelas, PR
Co., Inc.
425 Park Av.
New York, NY 10017
Continental Oil Co. (Conoco) Hebronville, MA
Petrochemicals Dept.
Saddle Brook, NJ 07662
Kearny, NJ
Bound Brook, NJ
Edison, NJ
Metuchen, NJ
Cartersville, GA
Richmond, CA
Perth Amboy, NJ
Newark, NJ
Crompton and Knowles
Corp.
345 Park Av.
New York, NY 10022
(continued)
Fair Lawn, NJ
Phthalic anhydride (III)
3,4-Oichloroanilme (III)
1,2-Dichloro-4-
nitrobenzene (III)
3,4-Dichloroaniline (III)*
1,2-Dichloro-4-nitrophenol
(III)*
3,4-Dichloroaniline (III)*
1,2-Dichloro-4-
nitrobenzene (III)*
o-Dichlorobenzene (III)*
Maleic anhydride (III)*
Phthalic anhydride (III)
Phthalic anhydride (III)*
1,2,4-Trichlorobenzene (III)*
Phthalic anhydride (III)*
Phthalic anhydride (III)*
Benzaldehyde (III)
316
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Diamond Shamrock Corp.
1100 Superior Av.
Cleveland, OH 44114
Dover Chem. Corp.
West 15th St.
Dover, OH 44622
Affiliate of ICC Industries,
Inc.
Dow Chem U.S.A.
2020 Dow Center
Midland, Ml
Cedartown, GA
Newark, NJ
Dover, OH
Kalama, WA
Midland, Ml
E.I. du Pont de Nemours
and Co., Inc.
1007 Market St.
Wilmington, DE 19898
Eastern Chem. Corp.
Now Eastern Chem. Div.
of Guardian Chem. Corp.
Eastman Kodak Co.
343 State St.
Rochester, NY 14650
Exxon Corp.
1251 Av. of the Americas
New York, NY 10020
Deepwater, NJ
Pequannock, NJ
Rochester, NY
Baton Rouge, LA
1-Phenol-2-sulfonic acid,
formaldehyde condensate
(III)*
2,4-Dichlorophenol (I)*
o-Dichlorobenzene (III)*
Hexachlorobenzene (III)*
1,2,4,5-Tetrachlorobenzene
(III)*
Tetrachlorobisphenol-A (II)*
1,2,4-Trichlorobenzene (III)*
Benzaldehyde (III)*
o-Chlorophenol (II)
2-Chloro-4-phenylphenol (II)
2,4-Dibromophenol (I)
o-Dichlorobenzene (III)
2,4-Dichlorophenol (I)
Pentabromochlorocyclo-
hexane (III)
Phenol (III)*, **
Phenyl ether (III)
Tetrabromobisphenol-A (II)
1,2,4,5-Tetrachlorobenzene
(III)
2,4,6-Tribromophenol (I)*
1,2,4-Trichlorobenzene (III)
o-Anisidine (III)
4-Chloro-2-nitrophenol (III)*
3,4-Dichloroaniline (III)
o-Dichlorobenzene (III)*
2-Nitro-p-cresol (III)*
o-Nitrophenol (III)*
o-Nitroanisole (III)
Chlorohydroqumone (II)*
2,4,6-Tribromophenol (I)*
o-Bromophenol (II)
Chlorohydroquinone (II)
2,5-Dihydroxybenzene-
sulfonic acid (III)*
2,5-Dinitrosahcylic acid |
Maleic acid (III)*
Phthalic anhydride (III)
(continued)
317
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Fairmount Chem. Co., Inc.
117 Blanchard St.
Newark, NJ07105
Fritzsche Dodge and Olcott,
Inc.
76 Ninth Av.
New York, NY 10011
GAF Corp
140 West 51st St.
New York, NY 10020
W. R. Grace and Co.
7 Hanover Square
New York, NY 10005
Great Lakes Chem. Corp.
Hwy. 52, Northwest
West Lafayette, IN 47906
Guardian Chem. Corp
230 Marcus Blvd.
Hauppauge, NY 11787
Hexcel Corp.
11711 Dublin Blvd.
Dublin, CA 94566
Hooker Chem. Corp
1900 St. James Place
Houston, TX 77027
Subsid. Occidental
Petroluem Corp.
Newark, NJ
Clifton, NJ
Rensselaer, NY
Fords, NJ
El Dorado, AR
Hauppauge, NY
Sayerville, NJ
Arecibo, PR
Niagara Falls, NY
Hummel Chem. Co., Inc.
P.O. Box 250
South Plainfield, NJ 07080
North Tonawanda, NY
South Shore, KY
Newark, NJ
South Plainfield, NJ
(continued)
2-Chloro-1,4-diethoxy-5-
nitrobenzene (II)
Benzaldehyde (III)*
Phenyl ether (III)*
2-Chloro-1,4-diethoxy-5-
nitrobenzene (II)
5-Chloro-2,4-dimethoxy-
anilme (II)
4-Chlororesorcinol (II)
Phthalic anhydride (III)*
Decabromophenoxy-
benzene (I)
Tetrabromobisphenol-A (II)
Chlorohydroquinone (II)*
2,4,6-Tribromophenol (I)
Pentabromoethylbenzene
(III)
Fumaric acid (III)
Phthalic anhydride (III)
o-Dichlorobenzene (III)*
Tetrachlorophthalic
anhydride (III)*
1,2,4,5-Tetrachlorobenzene
(III)*
1,2,4-Trichlorobenzene (III)*
Phenol (III)*, **
Phenol (III)*, **
2,4-Dinitrophenoxyethanol
(III)*
3,5-Dinitrosalicylic acid (III)*
Hexachlorobenzene (III)*
Picric acid (III)*
2,4-Dmitrophenoxyethanol
(Ml)
3,5-Dinitrosalicylic acid(lll)*
Hexachlorobenzene (III)*
Picric acid (III)*
Sodium picrate (III)
318
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
ICC Industries
See Solvent Chem.
Inmont Corp.
1133 Av. of the Americas
New York, NY 10036
Subsid of Carrier Corp.
International Mineral
and Chem. Corp.
IMC Plaza
Libertyville, IL 60048
Kalama Chemc, Inc.
The Bank of California
Center
Suite 1110
Kalama, WA
Kopper Co., Inc.
Koppers Bldg.
Pittsburgh, PA 1 5219
Martin Marietta Corp
6801 Rockledge Dr.
Bethesda, MD 20034
Maumee Chem. Co
Presumed to be acquired
by Sherwin Williams
Address not available
Mobay Chem. Co.
Penn Lincoln Pkwy. West
Pittsburgh, PA 15205
Monroe Chem. Co.
Saville Av. at 4th St.
Eddystone, PA
Subsid. of Kalama Chem.,
Inc. (see Kalama)
(continued)
Carlstadt, NJ
NOTE Carlstadt Plant
listed under Interchem-
ical Corp. which was
acquired by
Inmont Corp
Newark, NJ
Kalama, WA
3,5-Dichlorosalicylic acid
(I")*
Bridgeville, PA
Chicago, IL
Cicero,IL
Sodyeco, NC
St. Bernard, OH
New Martinsville, WV
Eddystone, PA
1,2,4-Trichlorobenzene (III)*
Benzaldehyde (III)
Maleic anhydride (III)
Phthalic anhydride (III)
Phthalic anhydride (III)*
Maleic anhydride (III)*
Phthalic anhydride (III)
2,6-Dibromo-4-nitrophenol
(ID*
3,4-Dichloroaniline(lll)*
1,2-Dichloroanilme (III)*
1,2-Dichloro-4-nitro-
benzene (III)*
2,4-Dmitrophenol (III)
Picric acid (III)
Sodium picrate (III)*
2,6-Dibromo-4-nitrophenol
(ID*
4-Chloro-2-nitrophenol (III)*
3,4-Dichlorophenyliso-
cyanate (III)
2,4-Dinitrophenol (III)
Benzaldehyde (III)
319
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Monsanto Co. Bridgeport, NJ
800 North Lindbergh Blvd.
St. Louis, MO 63166
Chocolate Bayou, TX
Monsanto (continued)
Luling LA
Sauget, IL
St Louis, MO
Texas City, TX
Henderson, NV
Montrose Chem Corp
of California
2401 Morris Av.
P.O. Box E
Union, NJ 07083
Jointly owned by
Chris Craft Industries, Inc.
and Stauffer Chem Co.
Morton Chem. Co., Div. Ringwood, IL
Morton-Norwich Products,
Inc
110 North Wacker Dr
Chicago, IL 60606
Nease Chem. Co., Inc.
P.O. Box 2.21
State College, PA 16801
Neville Chem. Co.
Neville Island
Pittsburgh, PA 15225
Northrop Corp.
1800 Century Park, East
Los Angeles, CA 90067
(continued)
State College, PA
Santa Fe Springs, CA
Asheville, NC
Phthalic anhydride (III)
Tetrachlorophthalic
anhydride (III)
Phenyl ether (III)
Phthalic anhydride (III)*
3,4-Dichloroanilme (III)
o-Chlorophenol (II)
3,4-Dichloroanilme (III)*
o-Dichlorobenzene (III)
1,2-Dichlor-4-nitrobenzene
(III)*
2,4-Dichlorophenol (I)
o-Nitroanisole (III)*
o-Nitrophenol (III)
o-Anisidine (III)*
Fumaric acid (III)
Maleic anhydride (III)
o-Nitroamsole (III)
o-Phenetidme (III)*
Phthalic anhydride (III)*
Phthalic anhydride (III)*
o-Dichlorobenzene (III)
3,5-Dnodosalicylic acid (II)*
2,5-Dihydroxybenzene-
sulfonic acid (III)*
2,5-Dihydroxybenzene-
sulfonic acid, potassium
salt (III)*
o-Dichlorobenzene (III)*
1,2,4-Tnchlorobenzene (III)*
Sodium picrate (III)
Tribromobenzene (III)
2,4,6-Trinitroresorcinol
320
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Northwest Industries
(See Velsicol)
G 300 Sears Tower
Chicago, IL 60606
Nyanza, Inc.
200 Sutton St.
North Andover, MA 01721
Occidental Petroleum Corp.
(See Hooker)
10889 Wilshire Blvd.
Suite 1500
Los Angeles, CA 90024
Olin Corp.
120 Long Ridge Rd.
Stamford, CT 06904
Ashland, MA
East Alton, IL
Mclntosh, AL
Rochester, NY
Ott Chem. Co.
See Story Chem.
PCR, Inc.
P.O. Box 1466
Gainesville, FL 32602
Petro-Tex Chem Corp
8600 Park Place
Houston, TX 77017
Jointly owned by
FMC Corp. and Tenneco,
Inc.
Pfister Chem., Inc.
Linden Av
Ridgefield, NJ 07657
(continued)
Gainesville, FL
Houston, TX
Newark, NJ
Ridgefield, NJ
3-Amino-5-chloro-2-
hydroxybenzenesulfonic
(III)
2-Amino-4-chloro-6-
nitrophenol (III)
2,4,6-Trinitroresorcinol (III)*
o-Dichlorobenzene (III)*
o-Bromofluorobenzene (III)
o-Chlorofluorobenzene (III)
3-Chloro-4-fluoromtro-
benzene (III)
2-Chloro-4-fluorophenol (I)
3-Chloro-4-fluorophenol(lll)
2,4-Dibromofluorobenzene
(III)
3,4-Difluoroaniline (III)
o-Difluorobenzene (III)
o-Fluoroanisole (II)
Pentachloroaniline (III)
Hexafluorobenzene (III)
Fumaric acid (III)*
Maleic anhydride (III)*
2-Chloro-1,4-diethoxy-5-
nitrobenzene (II)*
5-Chloro-2,4-dimethoxy-
aniline(ll)*
5-Chloro-2,4-dimethoxy-
anilme (II)
321
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Pfizer, Inc.
235 East 42nd St.
New York, NY 10017
Plastifax, Inc
Indust. Seaway Blvd.
P.O. Box 1056
Gulfport, MS 39501
PPG Industries, Inc.
One Gateway Center
Pittsburgh, PA 15222
Reichhold Chems., Inc
RCI Bldg.
White Plains, NY 10603
Rhodia, Inc.
600 Madison Av.
New York, NY 10022
F. Ritter and Co.
4001 Goodwin Av
Los Angeles, CA 90039
Rohm and Haas Co.
Independence Mall West
Philadelphia, PA 19105
R.S.A. Corp.
690 Saw Mill River Road
Ardsley, NY 10502
Salsbury Labs
2000 Rockford Road
Charles City, IA
Sherwin Williams Co.
101 Prospect Av.
Cleveland, OH 44101
Terre Haute, IN
Gulf Port, MS
Natrium, WV
Azusa, CA
Elizabeth, NJ
Morris, IL
Freeport, TX
Los Angeles, CA
Philadelphia, PA
Ardsley, NY
Charles City, IA
Chicago, IL
St. Bernard, OH
Fumaric acid I
1,2-Dichloro-4-nitro-
benzene (III)
o-Dichlorobenzene (III)
Phthahc anhydride (III)*
Maleic anhydride (III)
Phthalic anhydride (III)*
Fumaric acid (III)*
Maleic anhydride (III)
Phthalic anhydride (III)*
2,4-Dichlorophenol (I)
Benzaldehyde (III)*
1-Phenol-2-sulfonic acid,
formaldehyde condensate
(III)
Bromophenetole (II)
o-Bromophenol (II)
2,6-Diiodo-4-nitrophenol (II)
3,5-Diiodosalicylic acid (II)*
Pentabromophenol (I)*
2,4,6-Tnbromophenol (I)*
3,5-Dinitrosalicyclic acid (III)
2-Nitro-p-cresol (III)
Phthalic anhydride (III)*
2,6-Dibromo-4-nitrophenol
(ID*
4-Chloro-2-nitrophenol (III)*
Sobin Chems. Inc.
See International Minerals
and Chemicals Corp
(continued)
322
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Solvent Chem. Co., Inc.
720 Fifth Av.
New York, NY 10011
Affiliate of ICC Industries
Specialty Organics, Inc.
5263 North Fourth St.
Irwindale, CA 91706
Standard Chlorine Chem.
Co., Inc.
1035 Belleville Turnpike
Kearny, NJ 07032
Maiden, MA
Niagara Falls, NY
Irwindale, CA
Delaware City, DE
Kearny, NJ
Standard Oil Co. (California)
(See Chevron)
575 Market St.
San Francisco, CA 94105
Standard Oil Co. (Indiana)
(See Amoco)
910 South Michigan Av.
Chicago, IL 60605
Standard Oil Co (New Jersey)
(See Exxon)
Stauffer Chem. Co.
Westport, CT 06880
Stepan Chem. Co.
Edens and Winnetka Rd.
Northfield, IL 60093
Stering Drug, Inc.
90 Park Av.
New York, NY 10016
Story Chem. Corp.
500 Agard Rd.
Muskegan, Ml 49445
Ott Chem. Co., Div.
Sun Chem Corp.
Box 70
Chester, SC 29706
Edison, NJ
Nixon, NJ
Louisville, KY
Elwood, IL
Fieldsboro, NJ
Millsdale, IL
New York, NY
Muskegan, Ml
Chester, SC
o-Dichlorobenzene (III)*
1,2,4,5-Tetrachlorobenzene
(III)*
1,2,4-Trichlorobenzene (III)*
o-Dichlorobenzene (III)
2,3-Dichlorophenol (I)
2,6-Dichlorophenol (I)
o-Dichlorobenzene (III)
o-Dichlorobenzene (III)
1,2,4,5-Tetrachlorobenzene
(III)
1,2,4-Trichlorobenzene (III)
o-Dichlorobenzene (III)
1,2,4-Trichlorobenzene (III)*
Benzaldehyde (III)*
Benzaldehyde (III)*
Hexachlorobenzene (III)*
Phthalic anhydride (III)
Fumaric acid (III)*
Phthalic anhydride (III)*
1,2-Dihydroxy-3,5-
disulfonic acid, disodium
salt (III)*
3,4-Dichlorophenyliso-
cyanate (III)*
1,2,4-Trichlorobenzene (III)*
(continued)
323
-------
TABLE A4. (continued)
Producer
Location
Chemical (class)
Tenneco Chems. Co.
Park 80 Plaza, West
Saddle Brook, NJ 07662
Part of Tenneco, Inc.
Fords, NJ
Toms River Chem. Corp.
PO. Box 71
Toms River, NJ 08753
Owned by Ciba-Geigy 80%
and Sandoz AZ 20%
Transvaal, Inc.
Marshall Road
P.O. Box 69
Jacksonville, AR 72076
(Subsid. of Vertac)
Union Carbide Corp.
270 Park Av.
New York, NY 10017
UOP, Inc.
Ten UOP Plaza
Algonquin and
Mt. Prospect Roads
Des Plaines, IL60016
U.S Steel Corp.
Sixth and Grant
Pittsburgh, PA 15230
Velsicol Chem Corp.
341 East Ohio St
Chicago, IL 60611
Subsid. of Northwest
Industries, Inc.
Garfield, NJ
Toms River, NJ
Jacksonville, AR
Marietta, OH
East Rutherford, NJ
Neville Island, PA
Beaumont, TX
Chattanooga, TN
St. Louis, Ml
Benzaldehyde (III)*
3,4-Dichlorobenzaldehyde
(III)
3,4-Dichlorobenzotri-
chloride (III)
3,4-Dichlorobenzotn-
fluoride (III)*
Maleic anhydride (III)
Fumaric acid (III)
Benzaldehyde (III)
3-Amino-5-chloro-2-
hydroxybenzenesulfonic
acid (III)
2,4-Dichlorophenol (I)
Phenol (III)*, **
Benzaldehyde (III)
Fumaric acid (III)
Maleic anhydride (III)
Phthalic anhydride (III)
4-Bromo-2,5-dichloro-
phenol (I)
2,5-Dichlorophenol (I)
Benzaldehyde (III)*
Hexabromobenzene (III)*
Pentabromophenol (I)*
Tetrabromoblsphenol—A (II)
Tetrabromophthalic
anhydride (III)
Tribromobenzene (III)*
2,4,6-Tnbromophenol (I)*
(continued)
324
-------
TABLE A4. (continued)
Producer Location Chemical (class)
Vertac, Inc.
(See Transvaal)
2414 Clark Tower
Memphis, TN 38137
White Chem. Corp. Bayonne, NJ 2,4-Dibromophenol (I)
P.O. Box 278 Pentabromophenol (I)
Bayonne, NJ 07002 Pentabromotoluene (III)
2,4,6-Tribromophenol (I)
Whittaker Corp. San Diego, CA Hexafluorobenzene (III)*
10880 Wilshire Blvd. Pentafluoroaniline (III)*
Los Angeles, CA 90024 Chloropentafluorobenzene
(III)*
Tetrafluoro-m-phenylene-
diamine (III)*
Witco Chem. Corp Chicago, IL Phthalic anhydride (III)*
277 Park Av. Perth Amboy, NJ Phthalic anhydride (III)*
New York, NY 10017
*No longer produced at this location.
"From chlorobenzene
325
-------
TABLE A5. FORMER LOCATIONS OF ORGANIC CHEMICAL PRODUCTION
Producer
Location
Chemical (class)
Aldrich
Allied
Frankford, PA
Am. Aniline
Blue Spruce
Chem. Insecticide
Chem. Products
Chevron
Chris Craft
Commonwealth Oil
Conoco
Dover
Dow
Milwaukee, Wl
Buffalo, NY
Chicago, IL
Ironton, OH
Moundsville, WV
Syracuse, NY
Lock Haven, PA
Edison, NJ
Metuchen, NJ
Cartersville, GA
Richmond, CA
Perth Amboy, NJ
Newark, NJ
Penuelas, PR
Hebronville, MA
Dover, OH
Diamond Shamrock Cedartown, GA
Midland, Ml
Kalama, WA
2,4-Dichlorophenol (I)
3-Ammo-5-chloro-2-hydroxy-
benzenesulfonic acid (III)
Fumaric acid (III)
Maleic acid (III)
1-Phenol-2-sulfonic acid,
formaldehyde condensate (III)
Phthalic anhydride (III)
Phthalic anhydride (III)
Phthalic anhydride (III)
Phthalic anhydride (III)
Fumaric acid (III)
Maleic acid (III)
Maleic anhydride (III)
o-Dichlorobenzene (III)
o-Anisidine (III)
3,4-Dichloroaniline (III)
1,2-Dichloro-4-nitrobenzene (III)
3,4-Dichloroaniline (III)
1,2-Dichloro-4-nitrobenzene (III)
o-Dichlorobenzene (III)
Maleic anhydride (III)
Phthalic anhydride (III)
1,2,4-Trichlorobenzene (III)
Phthalic anhydride (III)
Phthalic anhydride (III)
o-Dichlorobenzene (III)
Hexachlorobenzene (III)
1,2,4,5-Tetrachlorobenzene (III)
Tetrachlorobisphenol-A (II)
Tetrachlorobisphenol-A (II)
1,2,4-Trichlorobenzene (III)
1-Phenol-2-sulfonic acid,
formaldehyde condensate (III)
Phenol (III)*
2,4,6-Tribromophenol (I)
Benzaldehyde (III)
(continued)
326
-------
TABLE A5. (continued)
Producer
Location
Chemical (class
du Pont
Deepwater, NJ
Eastern Chem.
(Currently Eastern
Chem. Div of Guardian)
Pequannock, NJ
Eastman Kodak
Fritzsche
W. R Grace
Guardian
Hooker
Hummel Chem
Inmont
(formerly
Interchemical Corp.)
Koppers
Martin Marietta
Rochester, NY
Clifton, NJ
Fords, NJ
Hauppauge, NY
Pequannock, NJ
Niagara Falls, NY
North Tonawanda, NY
South Shore, KY
Newark, NJ
South Plamfield, NJ
Carlstadt, NJ
Chicago, IL
Cicero, IL
Sodyeco, NC
4-Chloro-2-nitrophenol (III)
o-Dichlorobenzene (III)
2-Nitro-p-cresol (III)
o-Nitrophenol (III)
Chlorohydroquinone (II)
2,4,6-Tribromophenol (I)
2,5-Dihydroxybenzenesulfonic
acid (III)
Maleic acid (III)
Benzaldehyde (III)
Phenyl ether (III)
Phthalic anhydride (III)
Chlorohydroquinone (II)
Chlorohydroquinone (II)
2,4,6-Tribromophenol (I)
o-Dichlorobenzene (III)
Tetrachlorophthalic anhydride
(III)
1,2,4,5-Tetrachlorobenzene (III)
1,2,4-Trichlorobenzene (III)
Phenol (III)*
Phenol (III)*
2,4-Dinitrophenoxyethanol (III)
3,5-Dinitrosalicylic acid (III)
Hexachlorobenzene (III)
Picric acid (III)
3,5-Dinitrosalicylic acid (III)
Hexachlorobenzene (III)
Picric acid (III)
3,5-Dichlorosalicylic acid (III)
Phthalic anhydride (III)
Maleic anhydride (III)
2,6-Dibromo-4-nitrophenol (II)
3,4-Dichloroaniline (III)
1,2-Dichloro-4-nitrobenzene (III)
Sodium picrate (III)
(continued)
327
-------
TABLE AS. (continued)
Producer
Location
Chemical (class)
Monsanto
Morton Chem.
Nease Chem
Neville Chem.
Olin
Petro-Tex
Pfister
Reichhold
F. Ritter
R.S.A.
Sherwin Williams
Chocolate Bayou, TX
Sauget, IL
St. Louis, MO
Ringwood, IL
State College, PA
Santa Fe Springs, CA
East Alton, IL
Mclntosh, AL
Houston, TX
Newark, NJ
Azusa, CA
Elizabeth, NJ
Morris, IL
Los Angeles, CA
Ardsley, NY
St Bernard, OH
Sobin Chems. Newark, NJ
(currently International
Minerals and Chems.
Corp.)
Solvent Chem.
(continued)
Maiden, MA
Phthalic anhydride (III)
3,4-Dichloroanilme (III)
1,2-Dichloro-4-nitrobenzene (III)
o-Nitroanisole (III)
o Anisidme (III)
o-Phenetidine (III)
Phthalic anhydride (III)
3,5-Diiodosalicylic acid (II)
2,5-Dihydroxybenzenesulfonic
acid (III)
2,5-Dihydroxybenzenesulfonic
acid and potassium salt (III)
o-Dichlorobenzene (III)
1,2,4-Trichlorobenzene (III)
2,4,6-Trmitroresorcinol (III)
o-Dichlorobenzene (III)
Fumaric acid (III)
Maleic anhydride (III)
2-Chloro-1,4-diethoxy-5-
nitrobenzene (II)
5-Chloro-2,4-dimethoxyaniline
(M)
Phthalic anhydride (III)
Phthalic anhydride (III)
Fumaric acid (III)
Phthalic anhydride (III)
Benzaldehyde (III)
3,5-Diiodosahcylic acid (II)
Pentabromophenol (I)
2,4,6-Tnbromophenol (I)
2,6-Dibromo-4-nitrophenol (II)
4-Chloro-2-nitrophenol
(III)
Phthalic anhydride (III)
1,2,4-Trichlorobenzene (III)
o-Dichlorobenzene (III)
1,2,4,5-Tetrachlorobenzene (III)
1,2,4-Trichlorobenzene (III)
328
-------
TABLE A5. (continued)
Producer
Standard Chlorine
Stauffer
Stepan Chem.
Sterling Drug
Story Chem.
Sun Chem.
Tenneco
Union Carbide
Velsicol
Location
Kearny, NJ
Edison, NJ
Louisville, KY
Nixon, NJ
Fieldsboro, NJ
Millsdale, IL
New York, NY
Muskegan, Ml
Chester, SC
Fords, NJ
Marietta, OH
Chattanooga, TN
St. Louis, Ml
Chemical (class)
1 ,2,4-Trichlorobenzene (III)
Benzaldehyde (III)
Hexachlorobenzene (III)
Benzaldehyde (III)
Fumaric acid (III)
Phthalic anhydride (III)
1 ,2-Dihydroxy-3,5-disulfonic
acid, disodium salt (III)
3,4-Dichlorophenyhsocyanate
(Ml)
1 ,2,4-Trichlorobenzene (III)
3,4-Dichlorobenzotrifluoride (III)
Phenol (III)*
Benzaldehyde (III)
Hexabromobenzene (III)
Whittaker
Witco
San Diego, CA
Chicago, IL
Perth Amboy, NJ
Pentabromophenol (I)
Tribromobenzene (III)
2,4,6-Tnbromophenol (I)
Hexafluorobenzene (III)
Pentafluoroaniline (III)
Chloropentafluorobenzene (III)
Tetrafluoro-/r?-phenylenedia-
mine (III)
Phthalic anhydride (III)
Phthalic anhydride (III)
"From chlorobenzene.
329
-------
TABLE A6. PRODUCERS OF PESTICIDE CHEMICALS,
CLASSES I AND II
Chemical
Producer
Location
Class I
Bifenox
Chloranil
2,4-D and esters and salts
2,4-DB and salts
Dicamba
Dicapthon
Dichlofenthion
Mobil
Arapahoe
Uniroyal
Amchem
Chemical Insecticide
Corp.
Chempar
Diamond Shamrock
Dow
Fallek-Lankro
Guth Chem.
Imperial
Miller Chem
Monsanto
PBI-Gordon
Rhodia
Riverdale
Thompson Chem.
Thompson-Hayward
Transvaal
Woodbury
Amchem
Rhodia
Velsicol
American Cyanamid
Mobile
Dimethylamme salt of dicamba PBI-Gordon
Disul sodium (sesone) Amchem
(continued)
Mt. Pleasant, TN
Boulder, CO*
Naugatuck, CT*
Ambler, PA
Fremont, CA
St. Joseph, MO
Metuchen, NJ*
Portland, OR*
Newark, NJ*
Midland, Ml
Tuscaloosa, AL
Hillside, IL*
Shenandoah, IA
Whiteford, MD*
Sauget, IL*
Kansas City, KS
N. Kansas City, MO*
Portland, OR
St. Joseph, MO
St Paul, MN*
Chicago Hgts., IL
St. Louis, MO*
Kansas City, KS
Jacksonville, AR
Orlando, FL*
Ambler, PA
N. Kansas City, MO*
Portland, OR
St Joseph, MO
St Paul, MN*
Beaumont, TX
Chattanooga, TN*
Warners, NJ*
Charleston, SC*
Mt. Pleasant, TN*
Kansas City, KS
Ambler, PA*
Fremont, CA*
Linden, NJ*
St. Joseph, MO*
330
-------
TABLE A6. (continued)
Chemical
Producer
Location
2,4-DP
Erbon
Hexachlorophene
Isobac 20
Nitrofen
Pentachlorophenol (PCP) and
and salts
GAP
Union Carbide
Rhodia
Transvaal
Dow
Givaudan
Givaudan
Rohm and Haas
Dow
Merck
Monsanto
Reichhold
Sonford Chemical
Vulcan Materials
Linden, NJ*
Institute and South
Charleston, WV*
Portland, OR
Jacksonville, AR
Midland, Ml*
Clifton, NJ
Clifton, NJ
Philadelphia, PA
Midland, Ml
Hawthorne, NJ*
Sauget, IL
Tacoma, WA
Port Neches, TX*
Wichita, KS
Ronnel
Silvex and esters and salts
2,4,5-T and esters and salts
(continued)
Dow
Dow
Guth Chemical
Millmaster Onyx
Riverdale
Thompson-Hayward
Transvaal
2,4,5-T and esters and salts Amchem
2,3,4,6-Tetrachlorophenol
Chemical Insecticide
Corp
Chempar
Diamond Shamrock
Dow
Guth Chemical
Hercules
Millmaster Onyx
PBI-Gordon
Riverdale
Thompson Chemical
Thompson-Hayward
Transvaal
Dow
Sonford
Midland, Ml
Midland, Ml
Hillside, IL*
Berkeley Hgts , NJ*
Chicago Hgts., IL
Kansas City, KS
Jacksonville, AR
Ambler, PA
Fremont, CA
St. Joseph, MO
Metuchen, NJ*
Portland, OR*
Newark, NJ*
Midland, Ml
Hillside, IL*
Brunswick, GA*
Berkeley Hgts., NJ*
Kansas City, KS
Chicago Hgts., IL
St Louis, MO*
Kansas City, KS
Jacksonville, AR
Midland, Ml
Port Neches, TX*
(continued)
331
-------
TABLE A6. (continued)
Chemical
Producer
Location
2,4,5-Trichlorophenol
and salts
2,4,6-Trichlorophenol
Chemical Insecticide
Corp.
Diamond Shamrock
Dow
GAP
Hercules
Hooker
N. Eastern Pharmacy
Transvaal
Dow
Metuchen, NJ*
Newark, NJ*
Midland, Ml
Linden, NJ*
Brunswick, GA*
Niagara Falls, NY*
Verona, MO*
Jacksonville, AR
Midland, Ml
Class II
o-Benzyl-p-chlorophenol
Bromoxynil and esters
Carbophenothion
Chlorothalonil
DCPA
Dichlone
Dinitrobutylphenol,
ammonium salt
4,6-Dmitro-o-cresol and
sodium salt
loxynil
Lmdane
MCPA and derivatives
Monsanto
Reichhold
Amchem
Rhodia
Stauffer
Diamond Shamrock
Diamond Shamrock
Aceto
FMC
Uniroyal
Dow
Blue Spruce
Amchem
Rhodia
Hooker
Prentiss
Diamond Shamrock
Dow
Fallek-Lankro
Guth Chemical
Monsanto
Rhodia
Sauget, IL
Tacoma, WA
Ambler, PA
Portland, OR
St. Joseph, MO
Cold Creek, AL*
Henderson, NV
Greens Bayou, TX
Greens Bayou, TX
Flushing, NY*
Middleport, NY
Naugatuck, CT*
Midland, Ml
Bound Brook, NJ
Fremont, CA*
Portland, OR*
Niagara Falls, NY
Newark, NJ
Newark, NJ*
Midland, Ml
Tuscaloosa, AL
Hillside, IL*
Nitro, WV*
Portland, OR
(continued)
332
-------
TABLE A6. (continued)
Chemical
Producer
Location
MCPB
Mecoprop
Parathion
PCNB
Pipecolinopropyl-3,4-
dichlorobenzoate
Piperalin
Propanil
Tetradifon
2,3,6-Trichlorobenzoic acid
Amchem
Dow
Monsanto
Rhodia
Cleary
Fallek-Lankro
Morton Chem.
PBI-Gordon
Rhodia
American Cyanamid
American Potash
Monsanto
Stauffer
Velsicol
Monsanto
Olm
Eli Lilly
Eh Lilly
Blue Spruce
Eagle River
Monsanto
Sobm Chemical
FMC
Amchem
du Pont
Tenneco
2,3,6-Tnchlorophenyl acetic Amchem
acid and sodium salt
Tniodobenzoic acid
Tenneco
Amchem
Mallinckrodt
Ambler, PA
Fremont, CA
St. Joseph, MO
Midland, Ml*
Sauget, IL*
Portland, OR
St. Joseph, MO
Somerset, NJ
Tuscaloosa, AL
Ringwood, IL*
Kansas City, KS
Portland, OR
St. Joseph, MO
Warners, NJ*
Hamilton, MS*
Los Angeles, CA*
Anniston, AL
Mt. Pleasant, TN*
Bayport, TX*
Sauget, IL*
Leland, MS
Mclntosh, AL
Rochester, NY*
Lafayette, IN
Indianapolis, IN*
Lafayette, IN
Bound Brook, NJ
Helena, AR
Luling, LA*
Newark, NJ
Baltimore, MD*
Ambler, PA
Fremont, CA
St. Joseph, MO
Deepwater, NJ*
Fords, NJ*
Ambler, PA
Fremont, CA
St. Joseph, MO
Fords, NJ*
Ambler, PA
Raleigh, NC*
*No longer produced at this location
333
-------
TABLE A7. ALPHABETICAL LIST OF PESTICIDE CHEMICAL PRODUCERS
Producer
Location
Chemical (class)
Aceto Chem. Co., Inc. Flushing, NY
Alco Standard Corp.
(see Miller Chem.)
Amchem Products, Inc. Ambler, PA
Brookside Av.
P.O. Box 33
Ambler, PA 19002
(Subsid. of Union
Carbide)
Fremont, CA
Linden, NJ
St. Joseph, MO
American Cyanamid Co. Warners, NJ
Berdan Av.
Wayne, NJ 07470
American Potash and
Chem. Corp.
Kerr-McGee Chem.
Corp.
Kerr-McGee Center
Oklahoma City, OK
73125
Arapahoe Chem. Div.
Syntex Corp.
3401 Hillview Av.
Palo Alto, CA 94304
Blue Spruce Co
Stirling, NJ 07980
Hamilton, MS
Los Angeles, CA
Boulder, CO
Bound Brook, NJ
Dichlone (II)*
2,4-D and esters and salts (I)
2,4-DB and salts (I)
Disul sodium (I)*
2,4,5-T and esters and salts (I)
Bromoxynil and esters (II)
MCPB (II)
2,3,6-Trichlorobenzoic acid and
salt (II)
Triiodobenzoic acid (II)
2,4-D and esters and salts (I)
Disul sodium (I)*
2,4,5-T and esters and salts (I)
loxynil (II)*
MCPB (II)*
2,3,6-Trichlorophenyl acetic
acid, sodium salt (II)
Disul sodium (I)*
2,4-D and esters and salts (I)
Disul sodium (I)*
2,4,5-T and esters and salts (I)
MCPB (II)
2,3,6-Trichlorobenzoic acid (II)
2,3,6-Trichlorophenyl acetic
acid, sodium salt (II)
Dicapthon (I)*
Parathion (II)*
Parathion (II)*
Parathion (II)*
Chloranil (I)*
4,6-Dmitro-o-cresol and sodium
salt (II)
Propanil (II)
(continued)
334
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
Chemical Insecticide Metuchen, NJ
Corp.
30 Whitman Av.
Metuchen, NJ 08840
(1971 address)
Chempar Chem. Co., Portland, OR
Inc.
(address not available)
W A. Cleary
1049 Somerset St.
Somerset, NJ 08873
Somerset, NJ
Greens Bayou, TX
Diamond Shamrock
Corp
1100 Superior Av. Newark, NJ
Cleveland, OH 44114
Dow Chemical U.S.A. Midland, Ml
E. I. du Pont de Deepwater, NJ
Nemours and Co., Inc.
1007 Market St.
Wilmington, DE 19898
Eagle River Chemicals Helena, AR
Co.
Helena, AR 72342
(Subsid. of Vertac, Inc.)
Eli Lilly and Co. Indianapolis, IN
740 S. Alabama St. Lafayette, IN
Indianapolis, IN 96206
2,4-D and esters and salts (I)*
2,4,5-T and esters and salts (I)*
2,4,5-Tnchlorophenol (I)*
2,4-D and esters and salts (I)*
2,4,5-T and esters and salts (I)*
Mecoprop (II)
Chlorothalonil (II)
DCPA (II)
2,4-D and esters and salts (I)*
2,4,5-T and esters and
salts (I)*
2,4,5-Trichlorophenol and salts
in*
MCPA (II)*
2,4-D and esters and salts (I)
Dimtrobutylphenol ammonium
salt (II)
Erbon (I)*
MCPA and derivatives (II)
MCPB (II)*
Pentachlorophenol and salts (I)
Ronnel (I)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
2,4,5-Trichlorophenol (I)
2,4,6-Trichlorophenol (I)
2,3,6-Tnchlorobenzoic acid and
salts (II)*
Propanil (II)
Piperalin (II)*
Pipecolmopropyl-3,4-dichloro-
benzoate (II)
Piperalin (II)
(continued)
335
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
FMC Corp.
One Illinois Center
200 East Randolph Dr.
Chicago, IL 60601
Fallek-Lankro Corp.
P.O. Box H
Tuscaloosa, AL 35401
(Joint venture of Fallek
Chem Corp. and
Lankro Chem. Group
Ltd. [UK])
GAP Corp.
140 West 51st St
New York, NY 10020
Givaudan Corp.
100 Delawanna Av.
Clifton, NJ 07014
(Affiliate of
L. Givaudan and
Cie [Switz.])
Guth Chemical Co
P.O. Box 302
Naperville, IL
Gulf Oil Corp.
(see Millmaster Onyx)
Hercules, Inc
910 Market St.
Wilmington, DE 19899
Hooker Chemical Corp.
1900 St. James PI.
Houston, TX 77027
(Subsid. of Occidental
Petroleum Corp.)
Imperial, Inc.
West 6th and Grass
Streets
Shenandoah, IA
Mallinckrodt, Inc.
675 Brown Rd.
P.O. Box 5840
St. Louis, MO 63134
Baltimore, MD
Middleport, NY
Tuscaloosa, AL
Linden
Clifton, NJ
Hillside, IL
Brunswick, GA
Niagara Falls, NY
Shenandoah, IA
Raleigh, NC
Tetradifon (II)*
Dichlone (I)
2,4-D and esters and salts (I)
MCPA and derivatives (II)
Mecoprop (II)
Disul sodium (I)*
2,4,5-Trichlorophenol and salts
(I)*
Hexachlorophene (I)
Isobac 20 (I)
2,4-D and esters and salts (I)*
Silvex and esters and salts (I)*
2,4,5-T and esters and salts (I)*
MCPA (II)*
2,4,5-T and esters and salts (I)*
2,4,5-Trichlorophenol and salts
(I)*
2,4,5-Trichlorophenol and salts
(I)*
Lindane (II)
2,4-D and esters and salts (I)
Triiodobenzoic acid (II)*
(continued)
336
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
Merck and Co., Inc.
126 East Lincoln Av.
Rahway, NJ 07065
Hawthorne, NJ
Miller Chem. and Fertz. Whiteford, MD
Corp.
Subsid. of Alco
Standard Corp.
Valley Forge, PA 19481
Berkeley Hgts., NJ
Charleston, SC
Mt. Pleasant, TN
Millmaster Onyx Group
99 Park Av.
New York, NY 10016
(Part of Gulf Oil Corp.)
Mobil Chem Co.
Phosphorus Div.
P.O. Box 26638
Richmond, VA 23261
(Div of Mobil Corp.)
Monsanto Co Anniston, AL
800 North Lindbergh Lulmg, LA
Blvd. Nitro, WV
St. Louis, MO 63166 Sauget, IL
Monsanto Co.
(continued)
Morton Chem. Co. Ringwood, IL
Div. of
Morton-Norwich
Products, Inc.
100 North Wacker Dr.
Chicago, IL 60606
North Eastern Pharma- Verona, MO
ceutical and Chem. Co.
P.O. Box 270
Stamford, CT 06904
Occidental Petroleum
Corp. (see Hooker)
Olm Corp.
120 Long Ridge Rd.
Stanford, CT 06904
Leland, MS
Mclntosh, AL
Rochester, NY
Pentachlorophenol and salts (I)*
2,4-D and esters and salts (I)*
Silvex and esters and salts (I)*
2,4,5-T and esters and salts (I)*
Dichlofenthion (I)*
Bifenox (I)
Dichlofenthion (I)*
Parathion (II)
Propanil (II)*
MCPA (II)*
2,4-D and esters and salts (I)*
Pentachlorophenol and salts (I)
o-Benzyl-p-chlorophenol (II)
MCPB (II)*
PCNB (II)*
Mecoprop (II)*
2,4,5-Trichlorophenol and salts
(I)*
PCNB (II)
PCNB (II)
PCNB (II)*
(continued)
337
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
FBI-Gordon Corp. Kansas City, KS
300 South Third St
Kansas City, KS 66118
Prentiss Drug and Newark, NJ
Chem. Co., Inc.
363 Seventh Av.
New York, NY 10001
Reichhold Chem., Inc. Tacoma, WA
RCI Bldg.
White Plains, NY 10603
Rhodia, Inc.
600 Madison Av.
New York, NY 10022
(Subsid. of Rhone-
Poulenc SA [France])
Rhodia, Inc. (continued)
N. Kansas City, MO
Portland, OR
St. Joseph, MO
St. Paul, MN
Riverdale Chem., Inc. Chicago Hgts, IL
220 East 17th St.
Chicago Hgts., IL 60411
Sobin Chem., Inc. Newark, NJ
International Minerals
and Chem. Corp.
IMC Plaza
Lbertyville, IL 60048
Sonford Chem. Co.
Pure-Atlantic Hwy.
Port Neches, TX 77651
Stauffer Chem Co.
Westport, CT 06880
Port Neches, TX
Cold Creek, AL
Henderson, NV
Mt. Pleasant, TN
Dimethylamme salt of dicamba(l)
2,4,5-T and esters and salts (I)
Mecoprop (II)
Lindone (II)
Pentachlorophenol and salts (I)
o-Benzyl-p-chlorophenol (II)
2,4-D (I)*
2,4-DB (I)*
loxynil (II)*
2,4-D (I)
2,4-DB (I)
2,4-DP (I)
Bromoxynil and esters (II)
MCPA and derivatives (II)
MCPB (II)
Mecoprop (II)
2,4-D and esters and salts (I)
2,4-DB and salts (I)
Bromoxynil and esters (II)
MCPA and derivatives (II)
MCPB (II)
Mecoprop (II)
2,4-D and esters and salts (I)*
2,4-DB (I)*
2,4-D and esters and salts (I)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
Propanil (II)*
Pentachlorophenol and salts (I)*
2,3,4,6-Tetrachlorophenol (I)*
Carbophenothion (II)*
Carbophenothion (II)
Parathion (II)*
(continued)
338
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
Syntex Corp.
(see Arapahoe)
Tenneco Chems. Co. Fords, NJ
Park 80 Plaza West
Saddle Brook, NJ 07662
(Part of Tenneco, Inc.)
Thompson Chems. Corp. St. Louis, MO
3028 Locust St.
St. Louis, MO 63103
2,3,6-Trichlorobenzoic acid and
salts (II)*
(2,3,6-Trichlorophenyl)
acetic acid and sodium salt (II)*
2,4-D and esters and salts (I)*
2,4,5-T and esters and salts (I)*
Thompson-Hayward
Chem. Co
5200 Speaker Rd.
P.O. Box 2383
Kansas City, KS 66110
(Subsid. of North
American Philips Corp.)
Transvaal, Inc.
Marshall Rd.
P.O. Box 69
Jacksonville, AR 72076
(Subsid. of Vertac, Inc.)
Kansas City, KS
Jacksonville, AR
Union Carbide Corp.
270 Park Av.
New York, NY 10017
(see also Alchem)
Umroyal, Inc.
1230 Av. of the
Americas
New York, NY 10020
Velsicol Chem Corp.
341 East Ohio St.
Chicago, IL 60611
(Subsid of Northwest
Industries, Inc.)
Vertac, Inc.
(see Transvaal and
Eagle River)
Vulcan Materials Co.
P O. Box
Birmingham, AL 35223
(continued)
Institute and South
Charleston, WV
Naugatuck, CT
Bayport, TX
Beaumont, TX
Wichita, KS
2,4-D and esters and salts (I)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
2,4-D and esters and salts (I)
2,4-DP(l)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
2,3,4,6-Tetrachlorophenol (I)
2,4,5-Tnchlorophenol and
salts (I)
Disul sodium (I)*
Chloraml (I)*
DichlonedD"
Parathion (II)*
Dicamba (I)
Pentachlorophenol and salts (I)
339
-------
TABLE A7. (continued)
Producer
Location
Chemical (class)
Woodbury Chems.
Subsid of
Comutrix Corp
8373 N.E. 2nd Av.
Miami, FL33138
Orlando, FL
2,4-D and esters and salts (I)
*No longer produced at this location.
340
-------
TABLE A8. FORMER PESTICIDE PRODUCTION LOCATIONS
Producer
Aceto
Amchem
Location
Flushing, NY
Ambler, PA
Chemical (class)
Dichlone (II)
Disul sodium (1)
Fremont, CA
Linden, NJ
St. Joseph, MO
American Cyanamid Warners, NJ
American Potash Hamilton, MS
Arapahoe Boulder, CO
Chem. Insecticide Corp Metuchen, NJ
Chempar
Portland, OR
Diamond Shamrock Newark, NJ
Dow
du Pont
Eli Lilly
FMC
GAF
Guth Chem.
Hercules
(continued)
Midland, Ml
Deepwater, NJ
Indianapolis, IN
Baltimore, MD
Linden, NJ
Hillside, IL
Brunswick, GA
2,3,6-Trichlorobenzoic acid and
salts (II)
Disul sodium (I)
loxynil (II)
MCPB (II)
Disul sodium (I)
Disul sodium (I)
Dicapthon (I)
Parathion (II)
Parathion (II)
Chloranil (I)
2,4-D and esters and salts (I)
2,4,5-T and esters and salts (I)
2,4,5-Tnchlorophenol and salts
(I)
2,4-D and esters and salts (I)
2,4,5-T and esters and salts (I)
2,4,5-T and esters and salts (I)
2,4,5-Trichlorophenol and salts
(I)
MCPA(II)
Erbon (I)
MCPB (II)
2,3,6-Trichlorobenzoic acid and
salts (II)
Piperalin (II)
Tetradifon (II)
Disul sodium (I)
2,4,5-Trichlorophenol and salts
(I)
2,4-D and esters and salts (I)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
MCPA (II)
2,4,5-T and esters and salts (I)
2,4,5-Trichlorophenol and salts
(I)
341
-------
TABLE A8. (continued)
Producer
Location
Chemical (class)
Hooker
Mallinckrodt
Merck
Miller Chem.
Millmaster Onyx
Mobil
Monsanto
Morton
N Eastern Pharm
Olin
Rhodia
Sobm Chem
Sonford
Stauffer
Tenneco
Thompson Chem.
Union Carbide
Uniroyal
(continued)
Niagara Falls, NY
Raleigh, NC
Hawthorne, NJ
Whiteford, MD
Berkeley Hgts., NJ
Charleston, SC
Luling, LA
Nitro, WV
Sauget, IL
Ringwood, IL
Verona, MO
Rochester, NY
N. Kansas City, MO
Portland, OR
St. Paul, MN
Newark, NJ
Port Neches, TX
Cold Creek, AL
Fords, NJ
St Louis, MO
Institute and
South Charleston, WV
Naugatuck, CT
2,4,5-Tnchlorophenol and salts
(I)
Trnodobenzoic acid (II)
Pentachlorophenol and salts (I)
2,4-D and esters and salts (I)
Silvex and esters and salts (I)
2,4,5-T and esters and salts (I)
Dichlorofenthion (I)
Propanil (II)
MCPA(II)
2,4-D and esters and salts (I)
MCPB (II)
PCNB(II)
Mecoprop (I)
2,4,5-Tnchlorophenol and salts
(I)
PCNB (II)
2,4-D and esters and salts (I)
2,4-DB and salts (I)
loxynil (II)
2,4-D and esters and salts (I)
2,4-DB and salts (I)
Propanil (II)
Pentachlorophenol and salts (I)
2,3,4,6-Tetrachlorophenol (I)
Carbophenothion (II)
2,3,6-Tnchlorobenzoic acid and
salts (II)
(2,3,6-Trichlorophenyl) acetic
acid (II)
2,4-D and esters and salts (I)
2,4,5-T and esters and salts (I)
Disul sodium (I)
Chloranil (I)
Dichlone (II)
342
-------
TABLE A8. (continued)
Producer Location Chemical (class)
Velsicol Bayport, TX Parathion (II)
Chattanooga, TN Dicamba (I)
Woodbury Orlando, FL 2,4-D and esters and salts (I)
343
-------
APPENDIX B
LITERATURE REVIEW
This appendix is a compilation of references on dioxin analysis categorized by
sample matrix. The categories are given below:
Air Hexachlorobenzene
Biological tissue Insecticides
Blood Milk or cream
Commercial chlorophenols Plant material
Fats or oils Soil
Fish and crustaceans Urine
Flue gas Water
Fly ash Wipe samples
Grain Wood
Herbicide formulations
Air—
Oswald, E. 1979. Toxicology Research Projects Directory, Vol. 4, Iss. 7.
Biological Tissue—
Baughman, R., and M. Meselson. 1973. Environmental Health Perspectives, 5:27.
Bradlaw, J.A., et al. 1975. Proceedings of Society of Toxicology Meeting, Wil-
liamsburg, VA, March.
Freudenthal, J. 1978. In: Dioxin—Toxicological and Chemical Aspects, F. Cat-
tabeni, A. Cavallaro, and G. Galli, eds., SP Medical and Scientific Books, NY,
pp. 43-50.
Hass, J.R., et al. 1978. Anal. Chem. Vol. 50.
McKinney, J.D. 1978. In: Chlorinated Phenoxy Acids and Their Dioxins. Ecol.
Bull., 27:53-66.
O'Keefe, P.W. 1978. In: Dioxin—Toxicological and Chemical Aspects. F. Cat-
tabeni, A. Cavallaro, and G. Galli, eds., SP Medical and Scientific Books, NY,
pp. 59-78.
Oswald, E. 1979. Toxicology Research Projects Directory, Vol. 4, Iss. 7.
Rose, J.Q., et al. 1976. Toxicol. Appl. Pharmacol., 36:209.
Shadoff, L.A., and R.A. Hummel. 1978. Biomed Mass Spectrom, 5(1):7-13, Jan-
uary.
Tiernan, T.O. 1976. EPA Contract No. 68-01-1959. December.
Woolson, E.A., R.F. Thomas, and P.D.J. Ensor. 1972. J. Agric. Food Chem.,
20:351.
Woolson, E.A., et al. 1973. Advanced Chemistry Series.
Young, A.L. 1974. Report No. AFATL-TR-74-12, Air Force Armament Labor-
atory, Eglin Air Force Base, FL.
344
-------
Blood—
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1049-1053.
Oswald, E. 1979. Toxicology Research Projects Directory, Vol. 4, Iss. 7.
Commercial Chlorophenols—
Blaser, W.W., et al. 1976. Anal. Chem., 48:984.
Buser, J.R. 1975. J. Chromatography, 107:295.
Buser, J.R., and H.P. Bosshardt. 1976. Journal of the AOAC, 59:562.
Crummett, W.B., and R.H. Stehl. 1973. Environmental Health Perspectives, 5:15.
Firestone, D., et al. 1972. Journal of AOAC, 55:85.
Higginbotham, G.R., et al. 1968. Nature (London), 220:702.
Lamberton, J., et al. 1979. J. Amer. Ind. Hyg. Assoc., 40:816-822.
Langer, H.G., et al. 1971.162d Meeting, ACS, Washington, DC, Pest. Sec., No. 83.
Micure, J.P., et al. 1977. J. Chromatogr. Sci., 7:275.
Pfeiffer, C. 1976. J. Chromatogr. Sci., 14:386.
Pfeiffer, CD., T.J. Nestrick, and C.W. Kocher. 1978. Anal. Chem., 6:800.
Fats or Oils—
Campbell, T.C., and L. Friedman. 1966. Journal of the AOAC, 49:824.
Firestone, D. 1976. Journal of the AOAC, 59:323-325.
Firestone, D. 1977. Journal of the AOAC, 60:354-356.
Higginbotham, G.R., et al. 1967. Journal of the AOAC, 50:874.
Horwitz, W., ed. 1975. Official Methods of Analysis of the Association of Official
Analytical Chemists, Association of Official Analytical Chemists, Washington,
DC, 12th ed., Sect. 28.118, pp. 511-512.
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1049-1053.
Kocher, C.W., et al. 1978. Bulletin of Environmental Contamination and Toxi-
cology, 19:229.
O'Keefe, P.W., M.S. Meselson, and R.W. Baughman. 1978. Journal of the AOAC,
61:621-626.
Ress, J.R., G.R. Higginbotham, and D. Firestone. 1970. Journal of the AOAC,
53:628-634.
Shadoff, L.A., et al. 1977. Annali di Chimica, 67:583.
Shadoff, L.A., and R.A. Hummel. 1978. Bio. Mass Spec., 5:7.
Williams, D.T., and B.J. Blanchfield. 1971. Journal of the AOAC, 54:1429-1431.
Williams, D.T., and B.J. Blanchfield. 1972. Journal of the AOAC, 55:93-95.
Williams, D.T., and B.J. Blanchfield. 1972. Journal of the AOAC, 55:1358-1359.
FisK and Crustaceans —
Baughman, R.W., and M. Meselson. 1973. 166th Nat. Meeting, ACS, Chicago,
Abstract Pest., 55.
Baughman, R.W., and M. Meselson. 1973. Environmental Health Perspectives,
Expt. 5:27-35.
Baughman, R.W. 1974. Ph.D. Thesis, Harvard University, Cambridge, MA.
Fukuhara, K., et al. 1975. J. of Hyg. Chem., 21:318.
Gross, M.L. 1978. Personal communication. November.
Lamparski, L.L., T.J. Nestrick, and R.H. Stehl. Anal. Chem., 51(9):1453-1458.
Shadoff, L.A., and R.A. Hummel. 1975. 170th Nat. Am. Chem. Soc. Meeting,
Chicago, Ab. Anal., Vol. 80.
Shadoff, L.A., et al. Bull. Environ. Contam. Toxicol. In press.
345
-------
Flue Gas—
Frigerio, A., and M.C. Tagliabue. Impianti Incenerimento Rifuite Solidi: Prelievo,
Anal. Controllo Effluenti, [conv.]; 59-71.
Fly Ash—
Buser, H.R., H.P. Bosshardt, and C. Rappe. 1978. Chemosphere, 2:165.
Grain—
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1053-1099.
Isensee, A.R., and G.E. Jones. 1971. J. Agric. Food Chem., 19:1210.
Shadoff, L.A., and R.A. Hummel. 1978. Biomed Mass Spectrom, 5(1):7-13, Jan-
uary.
Herbicide Formulations—
Brenner, K.S., K. Muller, and P. Sattel. 1972. J. Chromatography, 64:39.
Brenner, K.S., K. Muller, and P. Sattel. 1974. J. Chromatography, 90:382-387.
Buser, H.R., and H.P. Bosshardt. 1974. J. Chromatography, 90:71.
Crummett, W.B., and R.H. Stehl. 1973. Environmental Health Perspectives, 5:15.
Edmunds, J.W., D.F. Lee, and C.M.L. Nickels. 1973. Pestic. Sci., 4:101.
Elvidge, D.A. 1971. Analyst (London), 96:721.
Hackins, J.N., D.L. Stalling, and W.A. Smith. 1978. Journal of the AOAC,61:32.
Hohmstedt, B. 1978. In: Dioxin—Toxicological and Chemical Aspects. F. Catta-
beni, A. Cavallaro, and G. Galli, eds., SP Medical and Science Books, NY, pp.
13-25.
Hughes, B.M., et al. 1975. Natl. Tech. Inform. Serv., AD-A011, 597:Vol. 1.
Polyhofer, K. 1979. Levensm Unters Forsch. 168(l):21-24, January.
Ranstad, T., N.H. Mahle, and R. Matalon. 1977. Anal. Chem., 49:386.
Rappe, C., H.R. Buser, and H.P. Bosshardt. 1978. Chemosphere, 5:431.
Shadoff, L.A., et al. 1978. Anal. Chem., 50(11):1586-1588.
Tiernan, T.O. 1976. EPA Contract No. 68-01-1959, December.
Tiernan, T.O., M.L. Taylor, and B.M. Hughes. 1975. Proceedings 1975 Interna-
tional Controlled Release Pesticide Symposium.
Vogel, H., and R.D. Weeren. 1976. Anal. Chem., 280:9.
Woolson, E.A., R.F. Thomas, and P.D. Ensor. 1972. J. Agric. Food Chem.,
20:351.
Hexach lorobenzen e—
Villanueva, E.C., et al. 1974. J. Agric. Food Chem., 22:916.
Insecticides—
Elvidge, D.A. 1971. Analyst, 96:721.
Storherr, R.W., et al. 1971. Journal of the AOAC, 54:218.
Webber, T.J.N., and D.J. Box. 1973. Analyst (London), 98:181.
Woolson, E.A., R.F. Thomas, and P.D.J. Ensor. 1972. J. Agric. Food Chem.,
20:351.
Shadoff, L.A., et al. Bull. Environ. Contam. Toxicol. In press.
Shadoff, L.A., and R.A. Hummel. 1978. Biomed Mass Spectrom, 5(1):7-13 Jan-
uary.
Milk or Cream—
Baughman, R., and M. Meselson. 1973. Environmental Health Perspectives, Exp.
Issue 5, 27-35.
Baughman, R.W. 1974. Ph.D. Thesis, Harvard University, Cambridge, MA.
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1049-1053.
346
-------
Plant Materials—
Buser, H.R. 1977. Anal. Chem., 49:918.
Buser, H.R. 1978. Monogr. Giovanni Lorenzini Found.; Vol 1, In: Dioxin—Toxi-
cological and Chemical Aspects. F. Cattabeni, A. Cavallaro, and G. Galli, eds.
SP Medical and Science Books, NY, pp. 27-41.
Di Domenico, A., et al. 1979. Anal Chem; 51(6):735-740.
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1049-1053.
Shadoff, L.A., and R.A. Hummel. Biomed Mass Spectrom, 5(1): 7-13, January.
Soil—
Bertoni, G., et al. 1978. Anal. Chem., 6:732.
Buser, H.R. 1977. Anal. Chem., 49:918.
Buser, H.R. 1978. Monogr. Giovanni Lorenzini Found.; Vol 1, In: Dioxin—Toxi-
cological and Chemical Aspects. F. Cattabeni, A. Cavallaro, and G. Galli, eds.,
SP Medical and Science Books, NY, pp. 27-41.
Camoni, I. 1978. J. of Chromatography, 153:233-238.
Di Domenico, A., et al. 1979. Anal Chem., 51(6):735-740.
Gross, M.L. 1978. Personal communication. November.
Hummel, R.A. 1977. J. Agric. Food Chem., 25:1049-1053.
Kearney, P.C., E.A. Woolson, and C.P. Ellington. 1972. Environ. Sci. Technol.,
1017.
Nash, R.G. 1973. Journal of the AOAC, 56:728.
Shadoff, L.A., and R.A. Hummel. 1975. 170th National American Chemical So-
ciety Meeting, Chicago, IL, Abst. Anal., 80.
Shadoff, L.A., et al. Bull. Environ. Contam. Toxicol. In press.
Shadoff, L.A., and R.A. Hummel. 1978. Biomed Mass Spectrom, 5(1):7-13,
January.
Widmark, G. 1971. Tracer Cosmos, a Realistic Concept in Pollution Analysis. In:
International Symposium on Identification and Measurement of Environ-
mental Pollutants, B. Westley, ed. National Research Council of Canada,
Ottawa, p. 396.
Woolson, E.A., et al. 1973. Advances in Chemistry Series, 120:112.
Urine—
Oswald, E. 1979. Toxicology Research Projects Directory, Vol. 4, Iss. 7.
Water—
Junk, G.A., et al. 1976. J. Am. Water Works Assoc., 68:218.
Shadoff, L.A., and R.A. Hummel. 1978. Biomed Mass Spectrom, 5(1):7-13,
January.
Wong, A. 1978. EPA Contract No. 68-03-2678, July.
Wipe Samples—
Di Domenico, A., et al. 1979. Anal. Chem., 51(6):735-740.
Erk, S.D., M.L. Taylor, and T.O. Tiernan. 1979. Chemosphere, 8(1):7-14.
Wood—
Hass, J.R., et al. 1978. Anal. Chem., 50:1474.
Levin, J.D., and C.A. Nilsson. 1977. Chemosphere, 7:443.
347
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INDEX
adrenaline, as natural dioxin precursor, 122
air, dioxin analysis of, 344
ammophenols, dioxins formed from, 121
bifenox, 63
reaction mechanism, 68
bioaccumulation of dioxins, 247-255
bioconcentration of dioxins, 247-255
biodegradation of dioxins, 230-233
biological methods of dioxin disposal:
micropit disposal, 269-270
soil conditioning, 268
wastewater treatment systems, 268-269
biological properties of dioxins, 189
biological tissue, dioxin analysis of, 344
biological transport of dioxins, 247-256
biomagnification of dioxins, 247-255
bithionol:
dioxins in, 108
manufacture, 108
blood, dioxins analysis of, 345
brominated phenols, 118-119
dioxins in, 119
manufacture, 118-119
4-bromo-2,5-dichlorophenol, reaction
mechanism, 44
capsaicin, as natural dioxin precursor, 122
carcinogenicity of dioxins, 227-229
of 2,3,7,8-TCDD, 216
catechol, as natural dioxin precursor, 122
chemical methods of dioxin disposal:
catalytic dechlorination, 267
chlorinolysis and chlorolysis, 266-267
chloroiodide degradation, 266
ozonolysis, 264-266
wet air oxidation, 266
chloracne, defined, 209
chloranil, reaction mechanism, 73
crustaceans, dioxin analysis of, 345
cytotoxicity of 2,3,7,8-TCDD, 221-222
2,4-D, 63
chemical formula, 92
as component of Herbicide Orange, 92
dioxins in, 55, 58, 94
human exposure, 174
manufacture, 93
producers, 94
reaction mechanism, 64
See also Herbicide Orange
2,4-DB, 63 '
dioxins in, 94
manufacture, 93-94
producers, 94
reaction mechanism, 65
decabromophenoxybenzene, reaction
mechanism, 46
2,4-DEP, 92, 94
dermatologic effects of 2,3,7,8-TCDD, 209-
210
detection of dioxins. See TCDD, detection
developmental effects of 2,3,7,8-TCDD,
214-216
2,4-dibromophenol, reaction mechanism, 47
dicamba, 63
dioxins in, 110-111
manufacture, 110-111
reaction mechanism, 70
dicapthon, reaction mechanism, 67
dichlofenthion, 63
reaction mechanism, 67
2,3-dichlorophenol, reaction mechanism, 48
2,4-dichlorophenol, reaction mechanism, 49
2,5-dichlorophenol, reaction mechanism, 50
2,6-dichlorophenol, reaction mechanism, 51
3,4-dichlorophenol, reaction mechanism, 52
2-chloro-4-fluorophenol, reaction mechanism, 2,4-dichlorophenoxyacetic acid. See 2,4-D
45
124,
chlorophenols and derivatives:
combustion of, and dioxin formation
130
commercial, dioxin analysis of, 345
manufacture, 81-86
producers, 86-88
production wastes, dioxins in, 112
as sources of dioxins, 78-112
colchine, as natural dioxin precursor, 123
combustion, formation of dioxins during,
121-128
combustion residues, dioxins in, 124-128, 130,
178
cream, dioxin analysis of, 346
4-(2,4-dichlorophenoxy)butyric acid.
See 2,4-DB
tris [2-(2,4-dichlorophenoxy)ethyl] phosphite.
See 2,4-DEP
2-(2,4-dichlorophenoxy) propionic acid.
See 2,4-DP
O-(2,4-dichlorophenyl) O-methyl isopropyl-
phosphoramidothioate See DMPA
dioxin analysis in specific samples.
air, 344
biological tissue, 344
blood, 345
commercial chlorophenols, 345
fats or oils, 345
fish and crustaceans, 345
348
-------
flue gas, 346
grain, 346
herbicide formulations, 346
hexachlorobenzene, 346
insecticides, 346
milk or cream, 346
plant material, 347
soil, 347
urine, 347
water, 347
wipe samples, 347
wood, 347
dioxin reaction, basic, 6
dioxins:
accumulation in plants, 255-256
bioaccumulation, 247-255
bioconcentration, 247-255
biodegradation, 230-233
biological properties, 189
biological transport, 247-256
biomagnification, 247-255
in bithionol, 108
in brominated phenols, 119
carcinogenicity, 227-229
in chlorophenols and derivatives, 78-112
in chlorophenol production wastes, 112
in combustion residues, 124-128, 130, 178
comparative lethal doses, 202-205
in 2,4-D, 55, 58, 93
in 2,4-DB, 94
detection. See TCDD, detection
disposal. See biological methods of dioxin
disposal; chemical methods of dioxin
disposal; disposal or destruction of
dioxins; physical methods of dioxin
disposal
in DMPA, 55, 96
in erbon, 55, 58, 62, 102-103
exposure. See exposure to dioxins
formation, 3-36
from aminophenols, 121
in chlorophenol manufacture, 84
from combustion, 121-128
from combustion of chlorophenols, 124,
130
from Irgasan DP 300, 111
from 0-nitrophenol, 120
from predioxins, 10, 35
genotoxicity, 216-222
gross and histopathologies caused by,
197-200
in hexachlorobenzene, 112, 116-118
in hexachlorophene, 105-106
laboratory preparation, 12-36
mutagenicity, 218-221, 229
organic chemicals as sources, 37-54
in pentachlorophenol, 84, 86
in pesticides, 55-77
photodegradation, 233-241
physical transport:
in air, 247
in soil, 241-246
in water, 246-247
in plastic, 128
precursors, 5-6
natural, 122-123
production for research purposes, 128-130
in ronnel, 55, 61, 104
in sesin, 109
in sesone, 55, 58, 62, 101-102
in silvex, 55, 58, 60, 101-102
structure, 3
in 2,4,5-T, 55, 58, 97
in 2,4,5-TCP, 89-91
in tetradifon, 55
in triclofenol piperazine, 110
toxicity, 187, 207
in wastewater, 172-173
See also TCDD; 2,3,7,8-TCDD
disposal or destruction of dioxins, 112
catalytic dechlorination, 267
chlorinolysis and chlorolysis, 266-267
chloroiodide degradation, 266
concentration, 260-263
by incineration, 258-260
micropit disposal, 269-270
microwave plasma, 260
molten-salt combustion, 259 260
ozonolysis, 264-266
photolysis, 263-264
radiolysis, 264
soil conditioning, 268
wastewater treatment systems, 268-269
wet air oxidation, 266
DMPA
dioxins in, 55, 96
producers, 96-97
structure, 96
DMSO, 27
2,4-DP, 63, 92
reaction mechanism, 66
drosophyllin A, as natural dioxin precursor,
123
embryotoxicity of 2,3,7,8-TCDD, 215-216
endocrine effects of 2,3,7,8-TCDD, 210-211
enzyme effects of 2,3,7,8-TCDD, 193-195
epidemiology of dioxin exposure, 223-229
erbon, 63
dioxins in, 55, 58, 62, 102-103
manufacture, 102-103
reaction mechanism, 62
eugenol, as natural dioxin precursor, 122
exposure to dioxins;
in chemical laboratories, 185-186, 223-224
from combustion residues, 178
epidemiology, 223-229
from foods, 175-178
from herbicide applications, 173-175
human, 223-229
from industrial accidents, 168-170, 224-226
occupational, 180-186
from pesticides, 178-179
public, 168-179
in related chemical industries, 183-185
from transportation accidents, 173
349
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from waste handling, 170-173, 224-225
in water supplies, 178
fats, dioxin analysis of, 345
fetotoxicity of 2,3,7,8-TCDD, 215-216,
226-227
fish, dioxin analysis of, 345
flue gas, dioxin analysis of, 346
foods, dioxins in, 175-178
fomecins, as natural dioxin precursors, 123
gas chromatography, principles of, 134-135
gas chromatography-mass spectrometry, used
in detection of dioxins, 140-167
gastrointestinal effects of 2,3,7,8-TCDD,
213-214
genotoxicity of dioxins, 216-222
glaucine, as natural dioxin precursor, 123
grain, dioxin analysis of, 346
gross and histopathologies caused by dioxins,
197-200
guaiacol, as natural dioxin precursor, 122
hematologic effects of 2,3,7,8-TCDD, 213
hepatic effects of 2,3,7,8-TCDD, 210
herbicide applications, exposure to dioxins
from, 173-175
herbicide formulations, dioxin analysis of, 346
Herbicide Orange (Agent Orange):
composition of, 92, 98
concentration in soil, 241-243
disposal, 248, 258-260, 263
exposure of military personnel, 185
health effects, 174, 226
hexachlorobenzene, 112-118
dioxin analysis of, 346
dioxins in, 112, 116-118
manufacture, 117-118
uses, 116-117
hexachlorophene:
dioxins in, 105-106
human exposures, 179, 226
manufacture, 105-106
reaction mechanism, 74
uses, 105
4-hydroxy-3-methoxymandelic acid, as
natural dioxin precursor, 123
1CMESA industrial accident. See Seveso
industrial accident
immunologic effects of 2,3,7,8-TCDD,
211-213
incineration, as disposal method for
hazardous wastes, 258-260
industrial accidents, exposure to dioxins
from, 168-170, 224-226
insecticides, dioxin analysis of, 346
Irgasan (TCS), 111
B5200, 111
DP-300, formation of dioxins from, 111
isopredioxin, defined, 8
lethal doses, comparative, for various
dibenzo-p-dioxins, 202-205
lipids, effects of 2,3,7,8-TCDD on, 195-196
mass spectrometry, principles, 135-138
metabolism of 2,3,7,8-TCDD, 188-196
microwave-plasma destruction of hazardous
wastes, 260
milk, dioxin analysis of, 346
molten-salt combustion, 259-260
mutagenicity of dioxins, 218-221, 229
naturally occurring dioxin precursors,
combustion of, 122-123, 131
neuropsychiatric effects of 2,3,7,8-TCDD, 214
N1OSH, 180
nitrofen, 63
reaction mechanism, 69
O-nitrophenol, dioxin formation from, 120
oils, dioxin analysis of, 345
organic chemicals:
Class I, 37
Class II, 37
Class III, 37
as sources of dioxins, 37-54
pathophysiology of 2,3,7,8-TCDD toxicity,
222
pentabromophenol, reaction mechanism, 53
pentachlorophenol, 9-11, 63
dioxins in, 84, 86
human exposure, 179, 183, 224
reaction mechanism (via hexachloroben-
zene), 72
reaction mechanism (via phenol), 71
uses, 78, 81
pesticides:
Class 1, 55-56
Class II, 55-57
dioxin exposures from, 178-179
as sources of dioxins, 55-77, 87, 97-111
pharmacokmetics and tissue distribution of
2,3,7,8-TCDD, 189-192
photodegradation of dioxins, 233-241
physical methods of dioxin disposal:
concentration, 260-263
photolysis, 263-264
radiolysis, 264
physical transport of dioxins:
in air, 247
in soil, 241-246
in water, 246-247
plant material, dioxin analysis of, 347
plants, accumulation of dioxins in, 255-256
porphyria cutanea tarda (PCT), defined, 209
predioxin, 6, 35-36
defined, 6
renal effects of 2,3,7,8-TCDD, 210
reserpine, as natural dioxin precursor, 123
ronnel, 103
dioxins in, 55, 61, 104
manufacture, 104-105
reaction mechanism, 61
safrole, as natural dioxin precursor, 122
salicylic acid, 120-!21
dioxins in, 120
manufacture, 120
producers, 121
350
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sesm:
dioxms in, 109
manufacture, 109
sesone, 63
dioxms in, 55, 58, 62, 94-95
manufacture, 94-95
reaction mechanism, 62
Seveso industrial accident:
concentration of dioxins in milk following,
251
concentration of dioxms in soil following, 244
concentration of dioxins in wildlife following,
248
decontamination, 259
degradation of dioxins in soil, 232
description of events, 168-170
health effects following, 225-226, 229
silvex:
dioxins in, 55, 58, 60, 101-102
human and animal exposure, 174
manufacture, 101-102
producers, 101
reaction mechanism, 60
Smiles rearrangement, 10, 35
defined, 10
soil, dioxin analysis of, 347
2,4,5-T:
as component of Herbicide Orange, 97
dioxins in, 55, 58, 97
human and animal exposure, 174-175,
223-224, 226-227
manufacture, 97-100
producers, 100
reaction mechanism, 59
TCDD, detection:
analytical methods, 139-141
by distillation, 133
by gas chromatography-mass spectrometry,
140-167
by mass spectrometry, 133-167
by PX21 powdered charcoal, 133
by resin sorption, 133
by thin-layer chromatography, 133
2,3,7,8-TCDD:
acute toxicity, 201-208
aquatic toxicity, 205-206
carcinogemcity, 216
chronic toxicity, 208-214
cytotoxicity, 221-222
dermatologic effects, 209-210
developmental effects, 214-216
effects on lipids, 195-196
embryotoxicity, 215-216
endocrine effects, 210-211
enzyme effects, 193-195
fetotoxicity, 215-216
gastrointestinal effects, 213-214
hematologic effects, 213
hepatic effects, 210
human exposure, 195-196
immunologic effects, 211-213
neuropsychiatric effects, 214
pathophysiology of toxicity, 222
renal effects, 210
structure, 4
teratogenicity, 214-215
See also dioxins; TCDD
2,4,5-TCP:
dioxins in, 89, 91
human exposure, 170-173, 180-183, 185,
226-227
manufacture, 88-91
production, 91-92
reaction mechanism, 59
uses, 88
teratogenicity of dioxins, 214-215, 226-227
2,3,4,6-tetrachlorophenol, 63
reaction mechanism, 75
tetradifon, dioxins in, 55
transportation accidents, exposure to dioxins
from, 173
transport of dioxins. See physical transport of
dioxins
2,4,6-tribromophenol, reaction mechanism, 54
2,4,5-trichlorophenol. See 2,4,5-TCP
2,4,5-trichlorophenoxyacetic acid. See 2,4,5-T
tnclofenol piperazine.
dioxins in, 110
manufacture, 110
urine, dioxin analysis of, 347
urushiol, as natural dioxin precursor, 122
vanillin, as natural dioxin precursor, 122
Viet Nam, exposure to dioxins of military
personnel. See Herbicide Orange
waste handling, exposure to dioxins through,
170-173, 224-225
wastewater, dioxins in, 172-173
water, dioxin analysis of, 347
water supplies, dioxins in, 178
wipe samples, dioxin analysis of, 347
wood, dioxin analysis of, 347
351
U.S. GOVERNMENT PRINTING OFFICE: 1980--757-Q64/0188
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