&EPA
United States
Environmental Protection
Agency
Industrial Environmental Research
Laboratory
Cincinnati OH 45268
EPA-600/2-80-156
June 1980
Research and Development
Dioxins
Volume
Sources, Exposure,
Transport, and
Contro
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a'maximum interface in related fields.
The nine series are:
1. Environmental Health Effects Research
2. Environmental Protection Technology
3. Ecological Research
4. Environmental Monitoring
5. Socioeconomic Environmental Studies
.6. Scientific and Technical Assessment Reports (STAR)
7. Interagency Energy-Environment Research and Development
8. "Special" Reports
9. Miscellaneous Reports
This report has been assigned to the ENVIRONMENTAL PROTECTION TECH-
NOLOGY series. This series describes research performed to develop and dem-
onstrate instrumentation, equipment, and methodology to repair or prevent en-
vironmental degradation from point and non-point sources of pollution. This work
provides the new or improved technology required for the control and treatment
of pollution sources to meet environmental quality standards.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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EPA-600/2-80-156
June 1980
DIOXINS:
VOLUME I.
SOURCES, EXPOSURE, TRANSPORT, AND CONTROL
by
M. P. Esposito, H. M. Drake,
J. A. Smith, and T. W. Owens
PEDCo Environmental, Inc.
Cincinnati, Ohio 45246
Contract No. 68-03-2577
Project Officer
David R. Watkins
Industrial Pollution Control Division
Industrial Environmental Research Laboratory
Cincinnati, Ohio 45268
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 (IERL-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.
n
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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 con-
trol methods be used. The Industrial Environmental Research Laboratory-
Cincinnati (lERL-Ci) assists in developing and demonstrating new and im-
proved methodologies that will meet these needs both efficiently and
economically.
This report is one of a three-volume series dealing with a group of
hazardous chemical compounds known as dioxins. The extreme toxicity of one
of these chemicals, 2,3,7,8-tetrachlorodibenzo-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 series the voluminous data on 2,3,7,8-TCDD and
other dioxins are summarized and assembled in a manner that allows compari-
son of related observations from many sources; thus, the series serves as a
comprehensive guide in evaluation of the environmental hazards of dioxins.
Volume I is a state-of-the-art review of dioxin literature. Detailed
information is presented on the chemistry, sources, degradation, transport,
disposal, and health effects of dioxins. Accounts of public and occupa-
tional exposure to dioxins are also included. Volume II details the devel-
opment of a new analytical method for detecting part-per-trillion levels of
dioxins in industrial wastes. It also includes a review of the analytical
literature on methods of detecting dioxins in various types of environmental
samples. Volume III identifies various routes of formation of dioxins in
addition to the classical route of the hydrolysis of chlorophenols. The
possible presence of dioxins in basic organic chemicals and pesticides is
addressed, and production locations for these materials are identified.
For further information, contact Project Officer David R. Watkins,
Organic and Inorganic Chemicals Branch, lERL-Ci. Phone (513) 684-4481.
David G. Stephan
Director
Industrial Environmental Research Laboratory
Cincinnati
m
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PREFACE
This report is Volume I in a series of three reports dealing with a
group of hazardous chemical compounds known as dioxins. This volume dis-
cusses the occurrence, environmental transport, and toxicity of this class
of compounds, and also summarizes the reported incidents of human exposure
to them and the techniques available for decontamination and disposal of
dioxin-contaminated material. Other volumes of this series examine ana-
lytical techniques used to identify the dioxins, the detailed chemistry of
dioxin formation, and the commercial products with potential for containing
dioxin contaminants.
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 series is
concerned not only with this compound, but also with all of its chemical
relatives that contain the dioxin nucleus. Throughout these reports, 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 tech-
nical confusion that has occasionally hindered comparison of information
from various sources. In particular, early laboratory analyses often re-
ported 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
series, 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.
IV
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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 volume reviews the extensive
amount of dioxin literature that has recently become available. 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. This is followed by a detailed examination of the indus-
trial sources of dioxins. Chemical manufacturing processes likely to give
rise to 2,3,7,8-TCDD and other dioxin contaminants are thoroughly discussed.
Other sources are also addressed, including incineration processes. Inci-
dents of human exposure to dioxins are reviewed and summarized. Reports on
possible routes of degradation and transport of dioxins in air, water, and
soil environments are characterized. Current methods of disposal of
dioxin-containing materials are described, and possible advanced techniques
for ultimate disposal are outlined. Finally, an extensive review of the
known health effects of 2,3,7,8-TCDD and other dioxins is presented. This
review emphasizes the results of recent toxicological studies of the effects
produced by chronic exposures and also the various possible mechanisms of
action for these toxicants.
This report was submitted in fulfillment of Contract No. 68-03-2577 by
PEDCo Environmental, Inc., under the sponsorship of the U.S. Environmental
Protection Agency. This report covers the period June 15, 1978 to January
6, 1980, and work was completed as of January 6, 1980.
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CONTENTS
Foreword iii
Preface iv
Abstract y
List of Figures viii
List of Tables x
Acknowledgment xii
List of Abbreviations xiii
I. Introduction 1
2. Chemistry 2
3. Sources 14
4. Routes of Human Exposure 77
5. Environmental Degradation and Transport 98
6. Disposal and Decontamination 131
7. Health Effects 147
References 200
Index 241
vii
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FIGURES
Number Page
1 Formation of Dioxins 7
2 Basic Chlorophenol Reactions 20
3 Direct Chlorination of Phenol 23
4 Flow Chart for 2,4,5-TCP Manufacture 30
5 Flow Chart for Hexachlorophene Manufacture 52
6 Locations of Current and Former Producers of Chlorophenols
and Their Derivatives 60
7 Map of Seveso Area Showing Zones of Contamination 79
8 Map of Test Area C-52A, Eg!in Air Force Base Reservation,
Florida 112
9 Diagram of Microagroecosystem Chamber 116
10 Farms at Which Cow's Milk Samples Were Collected for
TCDD Analysis in 1976 (July-August) 125
11 Schematic of Molten Salt Combustion Process 135
12 Schematic of Microwave Plasma System 137
13 Schematic for Ozonation/Ultraviolet Irradiation Apparatus 141
14 Internal View of Pesticide Micropit 146
15 Excretion of 14C Activity By Rats Following A Single Oral
Dose of 50 ug/kg (0.14 uCi/kg) 2,3,7,8-TCDD 153
16 Proposed Mechanism For Induction of AHH and Toxicity By
2,3,7,8-TCDD 156
17 Schematic of Rat Liver 13 Days After Administration of
2,3,7,8-TCDD 158
viii
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FIGURES (continued)
Number Page
18 Drawing of Tissue From Heart of Monkey Fed 2,3,7,8-TCDD;
Fixed With Formalin and Stained With Hematoxylin and
Eosin 160
19 Drawing of Heart Tissue From Monkey Fed 2,3,7,8-TCDD 161
20 Drawing of Section of Skin of Monkey Fed 2,3,7,8-TCDD 163
21 Drawing of Multinucleated Liver Cell From A Female Rat
Given 0.1 ug of 2,3,7,8-TCDD/kg/day For 2 Years 164
22 Drawing of Liver Tissue From Rat Fed 2,3,7,8-TCDD 165
23 Drawing of Normal Membrane Junctions From the Periportal
Region of A Test Animal 42 Days After Administration of
200 ug/kg 2,3,7,8-TCDD 166
24 Drawing of Distorted Periportal Membrane Junction,
Showing Loss of Continuity of Plasma Membranes
Between Parenchyma! Cells (42 Days After 200 ug/kg
2,3,7,8-TCDD) 167
25 Focal Alveolar Hyperplasia Near Terminal Bronchiole
Within Lung of Rat Given 2,3,7,8-TCDD At Dosage of
0.1 ug/kg Per Day 168
26 Lesion Classified Morphologically As Hepatocellular
Carcinoma In Liver of Rat Given 0.1 pg of 2,3,7,8-
TCDD/kg Per Day 185
27 Lesion Within Lung of Rat Given 0.1 ug of 2,3,7,8-TCDD/kg
Per Day 186
28 Linear Correlation of New South Wales Rate For Neural-Tube
Defects With Previous Year's Usage of 2,4,5-T In
Australia 197
ix
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TABLES
Number Page
1 Chlorinated Dioxins 4
2 Physical Properties of Two Chlorinated Dioxins 5
3 Chlorodioxins Reported in Chlorophenols 15
4 Commercial Chlorophenols and Their Producers 18
5 1977 Pentachlorophenol Production Capacity 25
6 Former 2,4,5-TCP Manufacturing Sites 32
7 'Current Basic Producers of 2,4-D and 2,4-DB Acids, Esters,
and Salts 37
8 Former Basic Producers of 2,4-D and 2,4-DB Acids, Esters,
and Salts 38
9 Derivatives of 2,4,5-Trichlorophenol and Their Recent (1978)
Producers 40
10 Former Producers of 2,4,5-T 44
11 Locations of Current and Former Producers of Chlorophenols
and Their Derivatives 61
12 Dioxins in Selected Samples 72
13 Sources of Purified Dioxin Samples for Research 76
14 Dioxins In Commercial Gelatin 88
15 Reported Incidents of Occupational Exposure To Dioxins During
Routine Chemical Manufacturing 92
16 Occupational Exposures To Dioxins Through Accidents In The
Chemical Manufacturing Industry 93
17 Industries Using Dioxin-Related Chemicals 95
18 Concentrations of Herbicide Orange and 2,3,7,8-TCDD In Three
Treated Test Plots 100
X
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TABLES (continued)
Number Page
19 Degradation of 2,3,7,8-TCDD In Soil 101
20 Photodegradation of 2,3,7,8-TCDD 104
21 Photodegradation of DCDD and OCDD 106
22 Concentrations of 2,3,7,8-TCDD at Utah Test Range 4 Years
After Herbicide Orange Applications 114
23 Concentrations of 2,3,7,8-TCDD at Eglin Air Force Base
414 Days After Herbicide Orange Application 114
24 TCDD Levels In Wildlife 119
25 TCDD Levels in Milk Samples Collected Near Seveso In July-
August 1976 124
26 Soil Application Rates and Replications 128
27 Toxicities of Selected Poisons 148
28 Biological Properties of Dioxins 150
29 Enzyme Induction 150
30 Body Burden of 14C Activity In Six Rats Given A Single Oral
Dose of 1.0 ng of [14C]-TCDD/kg 152
31 Toxicities of Organic Pesticides and 2,3,7,8-TCDD 170
32 Acute Toxicities of Dioxins 171
33 Acute Toxicities of 2,3,7,8-TCDD for Various Species 171
34 Summary of Acute Toxicity Effects of 2,3,7,8-TCDD 172
35 Effects of In Vivo 2,3,7,8-TCDD Exposure on Functional
Immunological Parameters 177
36 Summary of Neoplastic Alterations Observed In Rats Fed Subacute
Levels of 2,3,7,8-TCDD for 78 Weeks 183
37 Mutagenicity of Dioxin Compounds In Salmonella Typhimurium 187
38 Combined Rate of Neural-Tube Defects in New South Wales and
Previous-Year Usage of 2,4,5-T In Australia 196
xi
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ACKNOWLEDGMENT
This report was prepared by PEDCo Environmental, Inc., under the di-
rection of Richard W. Gerstle. M. Pat Esposito was the Project Manager and
principal investigator. Contributing authors included H. M. Drake, Jeffrey
A. Smith, M.D., and Timothy W. Owens. Additional technical assistance was
provided by Terrence W. Briggs, Ph.D., F. Howard Schneider, Ph.D., and A.
Christian Worrell of PEDCo, and Dr. Pat Sferra, EPA, lERL-Cincinnati. The
chemical figures used throughout this report series were provided by Walk,
Haydel & Associates. The hand renderings of photomicrographs in Section 7
of this volume were contributed by Lauren J. Smith.
The cooperation of the many organizations and individuals who assisted
in the collection of resource material is appreciated. In particular, we
acknowledge Battelle Columbus Laboratories, Columbus, Ohio, for their part
in the evaluation of disposal and decontamination technology. 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 assistance in gathering and clarifying points of informa-
tion for this document.
xii
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LIST OF ABBREVIATIONS
DBDD's
DCDD's
Dioxins
Hexa-CDD's
Hepta-CDD's
LD50
MCDD's
OCDD
PCP
Penta-CDD's
ppb
ppm
ppt
TBDD's
TCDD's
2,3,7,8-TCDD
TCP
Tri-CDD's
dibromodibenzo-p-dioxins
di chlorodi benzo-p-di oxi ns
dibenzo-p-dioxins
hexachl orodi benzo-p-di oxi ns
heptachlorodibenzo-p-dioxins
lethal dose to 50% of test group
monochlorodi benzo-p-di oxi ns
octachlorodibenzo-p-dioxin
pentachlorophenol
pentachlorodibenzo-p-dioxins
parts per billion (|jg/1 or ng/ml)
parts per million (mg/1 or pg/ml)
parts per trillion (ng/1 or pg/ml)
tetrabromodi benzo-p-di oxi ns
tetrachlorodi benzo-p-di oxi ns
2,3,7,8-tetrachlorodibenzo-p-dioxin
trichlorophenol
trichlorodibenzo-p-dioxins
xiii
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SECTION 1
INTRODUCTION
The growing concern with contamination of the environment by dioxins
arises principally from their toxicity and their widespread distribution as
contaminants of 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.
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 the chemical manu-
facture of chlorinated phenols and their derivatives.
Section 4 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 5 reviews the findings of these studies,
summarizing the known mechanisms of biodegradation, photodegradation,
physical transport, and 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 6.
Finally, Section 7 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 contam-
ination.
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
CHEMISTRY
A dioxin is any of a family of compounds known chemically as dibenzo-
para-dioxins. Each of these compounds has as a nucleus a triple-ring struc-
ture consisting of two benzene rings interconnected to each other through a
pair of oxygen atoms. The structural formula of the dioxin nucleus and the
convention used in numbering the substituent positions are as follows:
9 1
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 I 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-p-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-CDD1s)
10 isomers of hexachlorodibenzo-p-dioxin (Hexa-CDD's)
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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 character-
istics have been published (Buser, 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 differ-
entiated from each other (Buser, Bosshardt, and Rappe 1978; Buser 1975;
Rappe 1978).
The interest of health and environmental researchers in dioxins arose
principally because of the toxicity and distribution of one of these com-
pounds, 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; Crummett and Stehl 1973).
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-chloro-
phenol, 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 chloroben-
zenes 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 Volume III of this series. One route that has
been completely 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:
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TABLE 1. CHLORINATED DIOXINS
1-chloro a 1,2,3,4-
2-chloro a 1,2,3,6-
1,2-dichloro a 1,2,3,7-
1,3-dichloro a 1,2,3,8-
1,4-dichloro a 1,2,3,9-
1,6-dichloro a 1,2,4,6-
1,7-dichloro 1,2,4,7-
1,8-dichloro 1,2,4,8-
1,9-dichloro 1,2,4,9-
2,3-dichloro a 1,2,6,7-
2,7-dichloro a 1,2,6,8-
2,8-dichloro a 1,2,6,9-
1,2,3-trichloro a 1,2,7,8-
1,2,4-trichloro a 1,2,7,9-
1,2,6-trichloro 1,2,8,9-
1,2,7-tn'chloro 1,3,6,8-
1,2,8-trichloro 1,3,6,9-
1,2,9-trichloro 1,3,7,8-
1,3,6-trichloro 1,3,7,9-
1,3,7-trichloro a 1,4,6,9-
1,3,8-tn'chloro 1,4,7,8-
1,3,9-trichloro 2,3,7,8-
1,4,6-tn'chloro
1,4,7-tn'chloro
2,3,6-trichloro
2,3,7-trichloro a
•tetrachloro a
•tetrachloro
•tetrachloro
•tetrachloro a
•tetrachloro
•tetrachloro
tetrachloro
tetrachloro
tetrachloro
tetrachloro a
tetrachloro
tetrachloro a
tetrachloro a
tetrachloro
tetrachloro a
tetrachloro a
tetrachloro a
tetrachloro a
tetrachloro a
tetrachloro a
tetrachloro
tetrachloro a
1,2,3,4,6-
1,2,3,4,7-
1,2,3,6,7-
1,2,3,6,8-
1,2,3,6,9-
1,2,3,7,8-
1,2,3,7,9-
1,2,3,8,9-
1,2,4,6,7-
1,2,4,6,8-
1,2,4,6,9-
1,2,4,7,8-
1,2,4,7,9-
1,2,4,8,9-
1,2,3,4,6,
1,2,3,4,6,
1,2,3,4,6,
1,2,3,4,7,
1,2,3,6,7,
1,2,3,6,7,
1,2,3,6,8,
1,2,3,7,8,
1,2,4,6,7,
1,2,4,6,8,
1,2,3,4,6,
1,2,3,4,6,
Octachloro
pentachloro a
pentachloro a
pentachloro
pentachloro c
pentachloro
pentachloro a
pentachloro c
pentachloro
pentachloro
pentachloro
pentachloro
pentachloro a
pentachloro c
pentachloro
7-hexachloro a
8-hexachloro a
9-hexachloro a
8-hexachloro a
8-hexachloro a
9-hexachloro a
9-hexachloro b
9-hexachloro a
9-hexachloro a
9-hexachloro b
7,8-heptachloro a
7,9-heptachloro a
a
, Identified compounds.
One or the other of these compounds has been prepared.
, A mixture of these three compounds has been prepared.
The Dow Chemical Company has recently reported the synthesis of all 22
TCDD isomers.
4
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TABLE 2. PHYSICAL PROPERTIES OF TWO CHLORINATED DIOXINS
2,3,7,8-TCDD
OCDD
Empiric formula
Percent by weight C
0
H
Cl
Molecular weight
Melting point, °C
Decomposition temperature, °C
Solubilities, g/liter
o-dichlorobenzene
Chlorobenzene
Anisole
Xylene
Benzene
Chloroform
n-Octanol
Methanol
Acetone
Dioxane
Water
44.7
9.95
1.25
44.1
322
305
Above 700
1.4
0.72
0.57
0.37
0.048
0.01
0.11
0.0000002 (0.2 ppb)
31.3
7.0
61.7
459.8
130
Above 700
1.83
1.73
3.58
0.56
0.38
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2XY
This reaction indicates that a compound may be a dioxin precursor if it
meets two conditions:
0 The precursor compound must be an ortho-substituted benzene ring
in which one of the substituents includes an oxygen atom directly
attached to the ring.
0 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 substit-
uent, 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 et al. 1974; Jensen and Renberg 1972; Plimmer
1973; Buser 1978).
The basic dioxin reaction actually occurs in two steps. In the conden-
sation of 2,4,5-trichlorophenol, for example, one pair of substituents
reacts first to form a phenoxyphenate, or substituted diphenylether, in
accordance with the following reaction (Nilsson et al. 1974; Jensen and
Renberg 1972; Buser 1978; Moore 1979).
-------
0-CHLOROPHENOL POTASSIUM SALT
COPPER POWDER
CATALYST
»
IN WATER ANC
POTASSIUM HYDROXIDE
COPPER POWDER
CATALYST^
IN VACUUM _
SUBLIMATOR Cl
2.4-OICHLCROPHENOL POTASSIUM SALT
2,4,6-TRICHLOROPHENQL SODIUM SALT
Cl
ONa
2.4,5-TRlCHLDROPHENOL SODIUM SALT
UXSUBSTiTUTED 010IIN
CONDITIONS
UNREPORTED
Cl
VARIETY OF
CONDITIONS
COPPER POWDER
CATALYST^
IN VACUUM
SUBLIMATOR Cl
2,3,5.6-TETRACHLOfiOPHENOL POTASSIUM SALT
Cl Cl
I.2.4.6.7.9-HEXA-CDD
Cl
PENTACHLOROPHENOL
HEATING ONLY
OCDD
Figure 1. Formation of dioxins.
-------
Cl
ONa
NaCI
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).
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).
ONa
Cl Cl
ISOPREDIOXIN
The end product has been termed an "iso-predioxin" (Jensen and Renberg
1973). To this iso-predioxin, 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 iso-predioxin. Either of the iso-predioxins 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).
-------
Cl
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).
Cl
NaC1
NaOH
—^ NaCI + H2O
Cl
Cl
Another competing reaction that involves loss of chlorine is the reaction to
form dihydroxy chlorinated biphenyls (Jensen and Renberg 1973).
Cl
Cl
Cl
CI2
The chlorine thus released may react with other rings to form com-
pounds with higher chlorine saturation. Preparation of 2,3,7,8-TCDD was
accomplished by treatment of unsubstituted dioxin (World Health Organization
1977).
-------
Cl
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 decachloro-
diphenylether (Plimmer 1973).
Cl
+ HCI
HCI
Cl
Alternatively, the predioxin or the decachlorodiphenylether may lose chlo-
rine 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
CI2
These competing reactions are predominant only with acidic pentachloro-
phenol, however. Heating the sodium salt of pentachlorophenol produces OCDD
in essentially quantitative yield (World Health Organization 1977).
10
-------
Except for pentachlorophenol, once a predioxin is formed, there are
apparently no competing reactions other than its reversal into the pre-
cursor. In one test, when Irgasan DP-300, a predioxin (see Section 3 p.
57), 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 multi-ring structures, many of which are also toxic.
It has been more difficult to explain why dioxins other than the one pre-
dicted 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 spontan-
eously 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, espe-
cially 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 equilib-
rium 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
11
-------
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.
Since dioxins usually are formed only in low yields, the minimum condi-
tions leading to their formation are poorly defined. Heat, pressure,
catalytic action, and photostimulation 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; Cribble 1974; Buser 1978). As previously noted,
sodium pentachlorophenate is converted to essentially pure OCOD at approxi-
mately 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-chloronitrobenzenes 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
12
-------
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 arrange-
ment. 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 if it is bound to particulate 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 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).
13
-------
SECTION 3
SOURCES
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 re-
spect to their reported dioxin contaminants and their utilization, manu-
facture, production volumes, and derivatives. Similar information is pre-
sented, 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 are a 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 mono-
chlorophenols, six each of dichloro- and trichlorophenols, three tetra-
chlorophenols, and one pentachlorophenol. Many researchers have established
the presence of dioxins in these chemicals; Table 3 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 penta-
chlorophenol. 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 syn-
thesis of other organic compounds. Some of the less highly chlorinated
phenols are used with formaldehyde to make fire-resistant thermosetting
14
-------
TABLE 3. CHLORODIOXINS REPORTED IN CHLOROPHENOLS
Chlorophenol sample
Monochlorophenol
2-chlorophenol
o-chlorophenol
Dichlorophenol
2,4-di'chlorophenol
2, 6-di Chlorophenol
Trichlorophenol
2, 4, 5- tri Chlorophenol
(1969)
2, 4, 5- tri Chlorophenol
(1970)
2, 4, 5- tri Chlorophenol
(1970)
2, 4, 5-tri Chlorophenol
(1970)
Na- 2, 4, 5- tri Chlorophenol
(1967)
Na- 2, 4, 5- tri Chlorophenol
(1969)
2,4, 5- tri Chlorophenol
2, 4, 6- tri Chlorophenol
trichlorophenol
Tetrachlorophenol
2,3,4,6-tetrachlorophenol
(Dowicide 6)
2,3,4,6-tetrachlorophenol
2,3,4,6-tetrachlorophenol
(1967)
2,3,4,6-tetrachlorophenol
tetrachlorophenol
Chlorodioxins (-CDD's), ppma
mono-COD's
NO
-
NO
NO
NO
NO
ND
NO
NO
ND
-
ND
-
-
NO
NO
ND
-
OCDD's
ND
~
NO
ND
ND
NO
NO
ND
ND
3.72 (2,7)
-
ND
-
-
ND
ND
ND
-
tri-CDD's
ND
TCDD's
NO
penta-CDD's
ND
0.037 (2,3,7,8)"
ND
ND
NO
ND
ND
NO
ND
ND
-
93 (2,3,7)
-
-
ND
ND
ND
-
ND
ND
ND
ND
0.30 (1,3,6,8) ND
6.2 (2,3,7,8)
ND
ND
1.5
ND
0.07 (2,3,7,8) ND
ND
ND
1.4 (2,3,7,8) ND
0.3 (2,3,7,8) -
49 (1,3,6,8) ND
ND (0.5)
-
ND
NO
ND
ND (0.5)
-
-
ND
ND
ND
-
hexa-COD's
ND
-
ND
ND
ND
ND
ND
ND
ND
NO
-
ND
0.5-10
6
29
4. 1
ND
10-100
hepta-CDD's
ND
-
ND
NO
ND
ND
ND
ND
ND
ND
-
ND
0.5-10 0
-
OCDD
ND
-
ND
ND
ND
ND
ND
ND
ND
NO
-
ND
5-10
-
5.1 0.17
ND
•NO
ND
ND
10-100 10-100
Data source
Firestone '72
Chemical Week '79
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Elvidge '71
Firestone '72
Wool son et al. '72
Buser '75
Firestone '72
Firestone '72
Firestone '72
Wool son et al. '72
(continued)
-------
TABLE 3 (continued)
Chlorophenol sample
Pentachlorophenol
PCP (Dowicide 7)
PCP
Na-PCP (1967)
Na-PCP (1969)
PCP (1970)
PCP (1970)
PCP (1967)
PCP (1969)
PCP (1970)
PCP (1970)
PCP (1978)
Pentachl orophenate
PCP formulation
PCP (technical grade)
PCP (reagent grade)
PCP (many samples)
PCP's (17)
PCP or PCP-Na (7)
PCP (Oowicide 7 1970)
PCP (Dowicide 7 1970)
distilled
PCP
NaPCP (Oowicide G, 1978)
Chlorodioxins (-COD's), ppra3
mono-CDD' s
-
-
NO
NO
ND
NO
NO
ND
NO
ND
-
-
-
-
-
-
-
-
-
-
-
-
DCDD's
-
-
NO
ND
ND
ND
ND
NO
NO
NO
-
-
-
-
-
-
-
-
-
-
-
-
tri-CDD's
-
-
NO
NO
ND
ND
NO
ND
ND
ND
-
-
-
-
-
-
-
-
-
-
-
-
TCDD's
-
ND (0.5)
ND
NO
NO
ND
NO
NO
ND
NO
ND (0.1)
-
-
ND
ND
ND
-
-
-
-
-
-
penta-COD's
-
-
ND
NO
ND
NO
NO
ND
ND
ND
-
-
-
-
-
-
-
-
-
-
-
-
hexa-CDD's
9
10-100
14
20
39
35
0.17
13
0.91
15
19
-
-
33-42
0.02-0.03
9-27
0-23
0.03-10.0
4
1.0
9-27
ND-2
hepta-CDD's
235
100-1000
14.5
11.3
49
23
ND
47
2.1
23
140
•»-
870
19-24
0.04-0.09
90-135
-
0.6-180
125
6.5
-
1-12
OCDO
250
100-1000
3.8
3.3
15
ND
ND
ND
5.3
15
432
+
50-3300
7-11
D. 02-0. 03
575-2510
0-3600
5.5-370
2500
15
175-2510
4-173
Data source
Buser '75
Wool son '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Firestone '72
Oioxin in Industrial Sludges, '78
Jensen and Renberg '72
Jensen and Renberg ' 72
Villanueva '73
Villanueva '73
PCP - A wood preservative '77
Crummett '75
Buser and Basshardt '76
PCP Ad Hoc Study Kept. 12/78 SAB
PCP Ad Hoc Study Rept. 12/78 SAB
Johnson et al. '73
Dow Chemical Co. '78
Key to abbreviations and symbols:
ND = Not detected (minimum detection level, ppm). Other numbers in parenthesis indicate year Chlorophenol sample was obtained, or specific
dioxin detected.
. - Indicates not analyzed or not reported.
Presence of 2,3,7,8-TCDD confirmed but not quantitatively reported.
-------
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 produc-
tion 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
As a fungicide/siimicide 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)
As a 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 frac-
tional distillation, manufacturers selectively produce chlorophenols with
specific numbers and arrangements of chlorine atoms. Table 4 shows that 13
of the 19 possible chlorophenols are currently sold commercially in suffi-
cient 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.
17
-------
TABLE 4. COMMERCIAL CHLOROPHENOLS AND THEIR PRODUCERS'
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-Trichlorophenol
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.
18
-------
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, re-
chlorinations, 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 substi-
tuents with caustic, thereby replacing the chlorine atom with a hydroxyl
group (see Figure 2). 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).
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° 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
rearrangment 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.
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.
19
-------
DIRECT CHLORINATION
SOME
VARIATIONS
EMPLOY A
CATALYST
SOLVENT
UNNECESSARY
PHENOL
MIXTURE OF CHLOROPHENOLS
HYDROLYSIS
c.
Cl'
XCI CATALYST
UNNECESSARY
+ NaOH *-
^C| SOLVENT REQUIRED
Cl
POLYCHLORINATED BENZENE
SPECIFIC CHLOROPHENOL
Figure 2. Basic chlorophenol reactions.
20
-------
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 hydrol-
ysis 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 re-
claims 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.
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 tempera-
ture and therefore can be removed more easily in the filtration operations.
Chlorophenols can be purified by distillation to separate high-boil ing
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 hydrolys.is process are conducive to the formation of dioxin
compounds. Although not in present U.S. commercial use, the hydrolysis
manufacture of pentachlorophenol was especially favorable for the formation
of octachlorodibenzo-p-dioxin (OCDD). 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.
21
-------
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 there-
fore 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 chlo-
rinated phenols (see Figure 2), although certain compounds are formed pref-
erentially. 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 chloro-
phenols 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 3
(U.S. Patent Office 1960; Sittig 1969). Liquid phenol and/or lower chlo-
rinated 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 chlo-
ride, which is either used in other chemical operations or dissolved in
water to form substantially pure hydrochloric acid as I 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 pro-
portion 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).
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 dis-
tilled, with portions recycled to the first reactor for further chlori-
nation, or sold as is. 2,4-Dichlorophenol may be further processed to the
phenoxy herbicide 2,4-D.
22
-------
oo
CHLORINE
NONCONTACT HEATING
OR COOLING COILS
IN EACH VESSEL
CHLOROPHENOLS TO
PURIFICATION OR SALE
PHENOL
K
i
i
X
1
ALUMINUM
CHLORIDE
CATALYST
\ /
\ /
X
/
\
\
HYDROGEN
CHLORIDE
BYPRODUCT
Figure 3. Direct chlorination of phenol.
-------
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 of 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 1 of Volume 3 of this
series).
Dioxins have been reported in numerous samples of PCP, as shown in
Table 3. 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 chlori-
nation of phenol; apparently the method involving the hydrolysis of hexa-
chlorobenzene 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 Regula-
tion Reporter 1978). Details of Dow's process change were not reported.
Production—
Production figures for di- and tetra- chlorophenols are not available.
Although current figures for pentachlorophenol production are also not
available, it is estimated from production capacity information (Table 5)
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 4 indicates, chlorophenols are apparently manufactured by at
least 11 companies, which represent two diverse groups of chemical pro-
ducers. 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 chlori-
nation of phenol. Competitive with Dow in the sale of these seven chloro-
phenols 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 pro-
duction 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 rela-
tively low prices.
The other six chlorophenols are made by five companies that generally
manufacture fine or specialty chemicals:
24
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TABLE 5. 1977 PENTACHLOROPHENOL PRODUCTION CAPACITY3
Company
Dow Chemical U.S.A.5
Monsanto0
Reichold
Vulcan
Production
location
Midland, Mich.
Sauget, 111.
Tacoma, Wash.
Witchita, Kans.
1977 Capacity,
million of pounds
17
26
20
16
Total capacity 79
Source: American Wood Preservers Institute, 1977. These
figures presumably do not include production of sodium or
. potassium salts of pentachlorophenol.
Dow ceased production of the sodium salt of PCP (Dowicide G) in
April, 1978 (Dow Chemical Company 1978).
Monsanto stopped all PCP production as of January 1, 1978
(Dorman 1978).
25
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Velsicol Chemical Corp. - Beaumont, Texas
Eastman Kodak Company - Rochester, New York
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 con-
tract with specific industrial customers, sometimes to high standards of
purity. They are manufactured in much smaller quantities than those des-
cribed 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 descrip-
tion. 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 pro-
duction of m-chlorophenol in high yields, for example, general chemical
references describe a synthesis route that involves chlorination of nitro-
benzene, 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 com-
merical 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 chemi-
cals or chemical mixtures. Most often the trade name of the product changes
each time it is bought and sold.
26
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2,4,5-Trichlorophenol
In 1972, hexa-, hepta- and octachlorodioxins were found at concentra-
tions 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 3.
A U.S. EPA position document on 2,4,5-TCP (U.S. Environmental Protec-
tion Agency 1978i) 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 manu-
facture 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 in-
dustry to preseve 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 bacteri-
cide/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 in-
clude use on swimming-pool-related surfaces; household sickroom equip-
ment; 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.
27
-------
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 re-
chlorination 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 re-
chlorination of o-dichlorobenzene. Conversion of this chemical to the
sodium salt of 2,4,5-TCP is 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:
2NaOH
J.1 ^JL
Cl'
1.2.4.5-TETRACHLOROBENZENE
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 re-
action to completion. The first patented process (U.S. Patent Office 1950)
28
-------
uses a solvent of ethylene glycol or propylene glycol at preferred temper-
atures of 170° to 180°C and pressures up to 20 1b/in.2. 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 lb/in.2 (probably 50 to 200 lb/in.2). 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 lb/in.2. 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.
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 des-
cribed 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 4 is a flow chart
prepared from these sources, showing the most likely process details. In
this processing scheme, alcohol and caustic are mixed and heated. Tetra-
chlorobenzene 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-trichloro-
phenate (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. 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.
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 solu-
29
-------
1,2.4,5-
TETRACHLOROBENZENE
SODIUM-
HYDROXIDE
WATER-
AIR
EMISSION
EVAPORATION
ALCOHOL
RECYCLE
MIXING AND
PHASE
SEPARATION
TO
CONVERSION
PROCESS
TOLUENE
TOLUENE
+ IMPURITIES
DISTILLATION
.SOLID
WASTE
Na-2,4,5-TCP
IN WATER
HYDROCHLORIC
ACID
•-WASTEWATER
*-AIT( EMISSION
Figure 4. Flow chart for 2,4,5-TCP manufacture.
30
-------
tion 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, hydro-
chloric 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 Volume II of this
report series.)
As shown in Figure 4, 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 centri-
fuged 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 dis-
carded 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 (SRI 1979). Current records related to the EPA Federal Insec-
ticide, 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 6 by location
and owner. Details of the processes used by these former producers are
31
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TABLE 6. FORMER 2,4,5-TCP MANUFACTURING SITES'
Plant location
Owner
Niagara Falls, New York
Jacksonville, Arkansas
Verona, Missouri
Monmouth Junction, New Jersey
Linden, New Jersey
Chicago, Illinois
Cleveland, Ohio
Hooker Chemicals and Plastics
(approximately 45 years )
Reasor-Hill Corp. (1946-61)c
Hercules, Inc. (1961-71)C .
Transvaal, Inc. (1971-78) '
Vertac, Inc., Transvaal,
(subsidiary! (Nov. 1978-
March 1979)
Northeastern Pharmaceuticals and
Chemicals Co.
Rhodia, Inc.
GAF Corp.
Nalco Chemical Co.
Diamond Shamrock Corp.
Unless otherwise noted, the information in this table was derived
from Stanford Research Institute Directory of Chemical Producers,
U.S., 1976-1979, and U.S. International Trade Commission Synthetic
. Organic Chemicals, U.S. Production and Sales, 1968, 1974, 1976-78.
Chemical Week 1979a.
c Richards 1979a.
32
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not known; however, "toluene still bottoms" were said to be the source that
created a dioxin exposure at Verona, Missouri, which indicates that the
toluene washing step described above may have been used (see Section 4).
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 1978i). In 1970, the esti-
mated 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 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 deriva-
tives 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
herbicide 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.
2.4-0
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.
33
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In 1972, Wool son, 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.
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 chlorina-
tion 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 produc-
tion 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 chloro-
acetic 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 pro-
cedure 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).
34
-------
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 cap-
tured 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 below:
w
A
CH2CH2CH2COOH
O
NaOH
2.4-DICHLOROPHENOL
The ingredients are mixed and heated to a temperature of about 165°C
for a period that may range from 1 to 24 hours. On completion of the reac-
tion, 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 in this process by the
mixture of 2,4-dichlorophenol with sodium hydroxide being brought into
contact with a hot surface. 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.
35
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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
7. Former producers or production sites are listed in Table 8. No current
producers of 2,4-DEP are listed in the Stanford Research Institute publica-
tion 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 octachlorodioxins were detected (0.5 ppm detection
level). Analysis apparently was not performed for di-, tri-, or penta-
chlorodioxins.
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:
© © NaOH
CICH2CH2OSO3Na *
In more detail, the straight-chain reactant is made by combining
ethylene chlorohydrin and chlorosulfonic acid in a refrigerated water solu-
tion (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.
36
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TABLE 7. CURRENT BASIC PRODUCERS OF 2,4-D AND 2,4-DB
ACIDS, ESTERS, AND SALTS3
Pesticide
Company
Production location
2,4-D and esters
and salts
2,4-DB and salts
Dow Chemical Company
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
Rhodia, Inc.
Union Carbide Corp.
Amchem Products, Inc.
subsidiary
Midland, Michigan
Tuscaloosa, Alabama
Shenandoah, Iowa
Kansas City, Kansas
Kansas City, Kansas
Portland, Oregon
St. Joseph, Missouri
Chicago Heights, Illinois
Chicago Heights, Illinois
Ambler, Pennsylvania
Fremont, California
Jacksonville, Arkansas
Portland, Oregon
Ambler, Pennsylvania
Source: Stanford Research Institute 1978.
37
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TABLE 8. FORMER BASIC PRODUCERS OF 2,4-D AND 2,4-DB
ACIDS, ESTERS, AND SALTS
Pesticide formerly
reported produced
Company
Production location
2,4-D acid, esters,
and salts
2,4-DB and salts
Chempar
Miller Chemical
subsidiary of
Alco Standards
Rnodi a
Thompson Chemical
Woodbury, subsidiary
of Comutrix
Rhodia
Portland, Oregon
Whiteford, Maryland
North Kansas City, Kansas
St. Paul/Minneapolis, Minnesota
St. Louis, Missouri
Orlando, Florida
North Kansas City,
Missouri
St. Paul/Minneapolis, Minnesota
Source: Dryden et al. 1980 (Volume III of this report series).
38
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The manufacture of sesone meets all of the requirements for promotion
of the formation of 2,7-DCDD. 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 com-
mercial products containing the herbicide are currently registered as pesti-
cides with EPA.
DMPA--
The chemical name for DMPA is 0-(2,4-dichlorophenyl) 0-methyl iso-
propylphosphoramidothioate (Merck Index 1978). Some of the relatively
higher chlorodioxins (hexa-, hepta- and/or octachlorpdioxins) 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-dichlor-
ophenyl) phosphorodichloridothioate, which is made through the phosphorala-
tion 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 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 9 lists the known 2,4,5-TCP derivatives, their specific uses, and the
companies which have recently been reported to produce them.
39
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TABLE 9. DERIVATIVES OF 2,4,5-TRICHLORQPHENOL
AND THEIR RECENT (1978) PRODUCERS3
Derivative
Use
Current
producers
Production
location
2,4,5-T and
esters and
salts
Herbicide for
woody plant
control
Si 1 vex and
esters and
salts
(Fenoprop)
Herbicide for
woody plant
control; plant
hormone
Erbon
Herbicide,
weed and
grass killer
Ronnel Insecticide
(Fenchlorfos)
Hexachloro-
phene
Bactericide
Dow Chemical, U.S.A.
North American Phillips
Corp., Thompson-Hayward
Chemical Co. ,
subsidiary
FBI-Gordon Corp.
Riverdale Chemical Co.
Rhodia, Inc.
Union Carbide Corp.,
Amchem Products, Inc.
subsidiary
Vertac, Inc.
Transvaal, Inc.
subsidiary
Dow Chemical, U.S.A.
North American Phillips
Corp., Thompson-Hayward
Chemical Co.,
subsidiary
Riverdale Chemical Co.
Vertac, Inc. ,
Transvaal, Inc.,
subsidiary
Dow Chemical, U.S.A.'
Dow Chemical, U.S.A.
Givaudan Corporation
Midland, Michigan
Kansas City, Kansas
Kansas City, Kansas
Chicago Heights,
Illinois
Portland, Oregon or
St. Joseph, Missouri
Ambler, Pennsylvania
Fremont, California
St. Joseph, Missouri
Jacksonville,
Arkansas
Midland, Michigan
Kansas City, Kansas
Chicago Heights,
Illinois
Jacksonville,
Arkansas
Midland, Michigan
Midland, Michigan
Clifton, New Jersey
. Source: 1978 Directory of Chemical Producers, United States.
Rhodia is not listed in the 1978 Directory of Chemical Producers U.S.A.,
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.
In 1979 this company ceased production of 2,4,5-trichlorophenol for
. subsequent conversion to 2,4,5-T and silvex.
Although erbon is not listed in the 1978 Directory of Chemical
Producers, several companies including Dow Chemical have regis-
tered erbon pesticide products with EPA. Dow is most likely the
basic producer of the herbicide.
40
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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 con-
trolling 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 domes-
tic 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 (Wbolson, Thomas, and
Ensor 1972; Kearney et al. 1973b; Helling et al. 1973) of samples manu-
factured between 1950 and 1970 found 0.5 to 10 ppm TCDD's in 7 of 42 samples
tested; another 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.
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 University 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 commer-
cially 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.! (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:
41
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Cl
Cl
ONa
CICHaCOONa
Cl
Na-2.O-TCP
HCI
OCH2COONa
HCI
COOH
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-trichloro-
phenate is most often delivered to the process as a water solution contain-
ing excess sodium hydroxide directly from the Na-2,4,5-TCP manufacturing
process. Amy! 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-trichlorophenoxyacetate (Na-2,4,5-T) and sodium
chloride. The reaction proceeds under total reflux for about 1.5 hours at
110° to 130°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 dis-
solved in a sodium chloride brine.
The patent example incorporates a purification 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.
42
-------
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.
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 domes-
tically (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 Broad-
casting 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.
Eraulsifiable 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 10. Over a hundred companies were recently marketing more
than 400 formulated pesticide products containing 2,4,5-T (U.S. Environ-
mental Protection Agency 1978h).
Si 1 vex—Silvex is a family of compounds that act as hormones to plants
and can 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.
Silvex is available either as the acid or as 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 manu-
factured between 1965 and 1970 and analyzed in 1972; no other dioxins were
detected (Woolson, Thomas, and Ensor 1972; Kearney et al. 1973b).
43
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TABLE 10. FORMER PRODUCERS OF 2,4,5-T
(Prior to 1978)a
Company
Location
Chempar
Diamond-Shamrock
Hoffman-Taff, Inc.
Hercules, Inc.
Monsanto Co.
Rorer-Amchem
Wm. T. Thompson Co.,
Thompson Chemical Div.
Portland, Oregon
Cleveland, Ohio
Springfield, Missouri
Wilmington, Delaware
St. Louis, Missouri
Ambler, Pennsylvania
Fremont, California
St. Joseph, Missouri
Jacksonville, Arkansas
St. Louis, Missouri
Sources: SRI 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.
44
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The following are recent producers of silvex as listed in the 1978
Stanford Research Institute Directory of Chemical Producers:
Dow Chemical U.S.A. - 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. Environ-
mental Protection Agency 1978f).
Silvex manufacture is more complex than that of other 2,4,5-TCP deriva-
tives. 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. The figure below illustrates the most likely
chemical reaction that would form the silvex acid and also shows the sub-
sequent esterification, as described in the patent.
COOCH3
CH3-CH
OH 9
CH3CHCOOCH3
Cl
©fc)
NaOCH3
2,4.5-TCP
OC4H9
COOCH2CH2CH
AQUEOUS tCID
OC3H7
OC4H9
HOCH2CH2CH
OC3H7
H2SO4
SILVEX ESTER
SILVEX KID
45
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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 com-
pound 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 extrac-
tion using 1,2-dichloroethane to prepare the mixture for the next operation.
Si 1 vex 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 concen-
trated sulfuric acid as a reaction aid, the intermediate acid is mixed with
an ether alcohol. In the example shown on the previous page, butoxypropoxy-
propanol 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.
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 com-
pounds 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 tne degree of purification required by the various inter-
mediate compounds. Probably, as noted above, at least two solvent extrac-
tion 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).
46
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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 formu-
lators 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 iden-
tical to that used to make sesin. General organic chemical references in-
dicate 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:
CICH2CH2OH
NaOH
OCH2CH2OH
Cl
Cl
CH3CCI2COOH
H2S04
O
II
OCH2CH2O-C-CCI2CH3
47
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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 impuri-
ties.
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. 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 impuri-
ties 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.
Ronne1--The chemical name of ronnel is 0,0-dimethyl 0-(2,4,5-trichloro-
phenyl) phosphoroate. This insecticide is also known by such names as fen-
chlorfos, Trolene, Etrolene, Nankor, Korlan, Viozene, and Ectoral (Merck
Index 1978). 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
In the first step, dry Na-2,4,5-TCP is added to an excess of thio-
phosphoryl chloride (2 to 4 times the theoretical amount) and heated
48
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slightly, perhaps to 80°C. Sodium chloride is formed as an insoluble pre-
cipitate; it is filtered from the mixture and discarded. The clear filtrate
is vacuum-distilled to recover the excess thiophosphoryl chloride for re-
cycle 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 non-
reactive organic solvent is then used to extract the product from a mixture
of methanol, excess sodium methoxide, and byproduct sodium chloride. Suit-
able 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.
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.
Ronnel is reportedly produced by only one company - Dow Chemical Co. ,
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.
49
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Chlorophenol Derivatives With Unconfirmed Di'oxin 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-ll (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 ug/kg (<15 ppb) 2,3,7,8-TCDD (World Health Organization 1977). In a
1972 analysis, dioxins could not be detected in hexachlorophene at a detec-
tion limit of 0.5 mg/kg (0.5 ppm) (Helling et al. 1973).
Four process patents have been issued on manufacture of hexachloro-
phene, and all are variations of the following chemical reaction:
H2C=O
Cl
2,4.5-TCP
HEXACHLOROPHENE
50
-------
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°C over
a 24-hour period (U.S. Patent Office 1941). A second patent issued in 1948
discloses that the methanol solvent is eliminated and the reaction is con-
ducted 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 S03) is used as the catalyst and concen-
trated 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 5.
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 hexa-
chlorophene 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 produc-
tion 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. In a situation identical to that of the 2,4,5-T process, the
patent descriptions show the possiblity 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
51
-------
2,4,5-
TRICHLOROPHENOL CHLORINATED
HYDROCARBON
SULFURIC ACID- ' ' ^~
AND SO.
FORMALDEHYDE
REACTION
DECANTATION
ACTIVATED
CARBON
SULFURIC ACID
BYPRODUCT
CARBON
TREATMENT
CENTRIFUGATION
WASTE
SLUDGE
CHILLING
I
CENTRIFUGATION
1
DRYING
RECYCLE
RECYCLE
Figure 5. Flow chart for hexachlorophene manufacture.
52
-------
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 Givaudan1s primary supply of 2,4,5-TCP.
(For further details of the ICMESA incident see Section 4, p. 77.) 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 Volume II
of this series).
.About 400 commercial products containing hexachlorophene have been
marketed recently in pesticide, drug, cosmetic, and other germicidal formu-
lations. The annual production volume of the germicide is not reported.
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 Admin-
istration. 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-dichlorophenpl 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 belov,.
SCI2
AICI3
BITHIONOL
53
-------
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 operation 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.
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 on the following page (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.
A process patent discloses that the second reaction step is a combina-
tion 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 re-
cycle and possibly to separate the product from any impurities.
54
-------
OH
OCH2CH2OH
NaOH
Cl
2.4-DICHLOROPHENOL
OCH2CH2O-C—('
SESIN
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 ordi-
narily 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.
Triclofenol Piperazine--
A pharmaceutical compound can be made from commercial 2,4,5-trichloro-
phenol for use as an anthelmintic (deworming medication) (U.S. Patent Office
1961a; 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
55
-------
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 chemi-
cally 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 theo-
retical ly possible, however.
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.
O
II
Cl HO-C
CH3OSO3CH3
NaOH
OCH3
DICMBI
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 tempera-
ture 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).
56
-------
On completion of the reaction, the mixture is acidified with hydro-
chloric 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 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 Chlorophenol Derivatives—
Compounds other than the
dioxin sources, but are made and
products listed above are
used in smaller volumes.
also potential
A compound with the trade name of Irgasan B5200 is used as a bacterio-
stat 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
control the sea .lamprey, an eel-like fish.
formulation was 3,4,6-trichloro-2-nitrophenol,
fo11ows:
used in the Great Lakes to
The active ingredient of the
whose chemical formula is as
57
-------
This compound was made by direct nitration of 2,4,5-trichlorophenol 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:
It was probably made by acylation of 2,4,6-trichlorophenol with dimethyl
sulfate.
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 hexachloro-
phene. 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 concen-
trations 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 Volume II of this series).
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 sam-
ples 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 chloro-
phenol ic 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.
58
-------
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 un-
doubtedly be quite concentrated and potentially very dangerous. 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
6 illustrates the locations where chlorophenols and their derivatives are
now or were formerly produced. A list of these locations is presented in
Table 11; note that this list does not include locations of the many com-
panies 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 6. Additional information related to the environmental
effects of dioxin disposal is presented in the subsection on Water Transport
in Section 5.
HEXACHLOROBENZENE
In 1974, a technical paper reported the presence of OCDD in samples of
commercial hexachlorobenzene (Villaneuva et al. 1974). Three samples were
analyzed, two of which contained OCDD in concentrations of 0.05 and 211.9
ppm. All three contained octachlorodibenzofuran (OCDF) in concentrations of
0.34, 2.33, and 58.3 ppm. One sample contained a trace amount of hepta-
chlorodibenzofuran. 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
1-Pentachlorophenyl-l,2,3-dichloroethylene
Decachlorobiphenyl
59
-------
1. PHILADELPHIA, PA.
2. SAN MATEO, CAL.
3. PORTLAND, OREG.
4. CLEVELAND, OHIO
5. MIDLAND, MICH.
6. TUSCALOOSA, ALA.
7. LINDEN, N.J.
8. CLIFTON, N.J.
9. NAPERVILLE, ILL.
10. JACKSONVILLE, ARK.
11. SPRINGFIELD, MO.
12. NIAGARA FALLS, N.Y,
13. DOVER, OHIO
14. SHENANDOAH, IOWA
15. RAHWAY, N.J.
16. WHITEFORD, MD.
17. SAUGET, ILL.
18. CHICAGO, ILL.
19. KANSAS CITY, KANS.
20. VERONA, MO.
21. TACOMA, WASH.
22. ST. PAUL, MINN.
23. ST. JOSEPH, MO.
24. CHICAGO HEIGHTS, ILL.
25. NITRO, W. VA.
26. AMBLER, PA.
27. FREMONT, CAL.
28. PORT NECHES, TEX.
29. ST. LOUIS, MO.
30. WICHITA, KANS.
31. ORLANDO, FLA.
Figure 6. Locations of current and former producers of
chlorophenols and their derivatives.
60
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TABLE 11. LOCATIONS OF CURRENT AND FORMER PRODUCERS OF
CHLOROPHENOLS AND THEIR DERIVATIVESa
Producer
Location
Chemical Type
Alco Chemical Corp.
J. H. Baxter and Company
Chempar
Diamond Shamrock Corp.
Dow Chemical, U.S.A.
Fallek-Lankro Corp
GAP
Givaudan Corporation
Chemicals Division
Guth Corp.
Hercules, Inc.
Hoffman-Taft, Inc.
Hooker Chemical Corp.
Occidental Petroleum
Corp., subsidiary
Philadelphia,
Pennsylvania
San Mateo, California
Portland, Oregon
Cleveland, Ohio
Midland, Michigan
Tuscaloosa, Alabama
Linden, New Jersey
Clifton, New Jersey
Naperville, Illinois
Jacksonville, Arkansas
Springfield, Missouri
Niagara Falls, New York
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
Si 1 vex
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
(continued)
61
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TABLE 11 (continued)
Producer
Location
Chemical Type
ICC Indus., Inc.
Dover Chem. Corp.,
subsidiary
Imperial, Inc.
Merck and Co., Inc.
Miller Chemicals
Alco Steel subsidiary
Monsanto Company
Monsanto Industrial
Chemicals Company
Nalco Chemical Co.
North American Phillips
Corp., Thompson-Hayward
Chemical Co., subsidiary
North Eastern
Pharmaceuticals
PBI-Gordon Corporation0
Private Brands, Inc.c
Reichhold Chemicals, Inc.
Rhodia, Inc.
Agricultural Division
Riverdale Chemical Co.
Roberts Chemicals, Inc.
Rorer-Amchem
Dover, Ohio
Shenandoah, Iowa
Rahway, New Jersey
Whiteford, Maryland
Sauget, Illinois
Chicago, Illinois
Kansas City, Kansas
Verona, Missouri
Kansas City, Kansas
Kansas City, Kansas
Tacoma, Washington
Portland, Oregon
St. Paul, Minnesota
St. Joseph, Missouri
Chicago Heights,
Illinois
Nitro, West Virginia
Ambler, Pennsylvania
Amchem Products, Inc., Div. Fremont, California
I St. Joseph, Missouri
(continued)
PCP
2,4-D
2,4,5-TCP
2,4-D
PCP
2,4,5-T
2,4-D
PCP
2,4,5-TCP
2,4-D
2,4,5-T
Si 1 vex
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
Si 1 vex
2,4,6-TCP
2,4,5-T
2,4-D
62
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TABLE 11 (continued)
Producer
Location
Chemical Type
Sanford Chemicals
Thompson Chemicals
Union Carbide Corp.
Agricultural Products
Division
Amchem Products, Inc.,
subsidiary
Vertac, Inc.
Transvaal ,blnc.,
subsidiary
Vulcan Materials Co.
Chemicals Division
Woodbury
Comutrix subsidiary
Port Neches, Texas
St. Louis, Missouri
Ambler, Pennsylvania
Fremont, California
St. Joseph, Missouri
Jacksonville,
Arkansas
Wichita, Kansas
Orlando, Florida
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.
Si 1 vex
PCP
2,4-D
Sources: SRI 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
Chemicals, United States Production and Sales. 1974,
b 1976, 1977, and 1978.
Hercules, Inc., was a former owner of the Jacksonville, Arkansas,, facility
c now owned by Vertac, Inc.
Private Brands, Inc., is believed to be a former owner of the Kansas City,
^ Kansas, facility now owned by PBI-Gordon Corp;
Former Rorer-Amchem facilities in Ambler, Pennsylvania; Fremont, California;
and St. Joseph, Missouri, are now owned by Union Carbide Corp.
63
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Octachlorobipheny1ene
Octachoro-1,1-bicyclopentadienylidene
Hexachlorocyclopentadiene
Nonachlorobipheny1
Decachlorobipheny1
Pentachloroi odobenzene
Heptachloropilium
It is significant that this list includes no phenolic compounds and no
predioxins or iso-predioxins. 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. Benzene hexachloride (BHC) is the common name of hexa-
chlorocyclohexane. Its empiric formula is C6H6C16, and its structure re-
sults from direct addition of chlorine to benzene rather than from replace-
ment 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 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 chloro-
sulfonic acid or sulfuryl chloride and holding the mixture at approximately
200°C for several hours (U.S. Patent Office 1957a). This step removes the
64
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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
CI,
U.V. LIGHT
BENZENE
BHC
CISO3H
HEXACHLOROBENZENE
Decriptions of these process steps provide no indication that dioxins
are formed. The raw materials are benzene, chlorine, and chlorosulfonic
acid, none of which are likely sources of dioxins. The only reactant that
could contribute the oxygen needed to complete the dioxin ring is chloro-
sulfonic acid, but in this compound the oxygen is tightly bound in a linkage
with sulfur.
There is, however, a supplemental process that contributes other chemi-
cals 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 for the sale of gamma-BHC as an insecticide, this material is extrac-
ted 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 re-
filtered. 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 supple-
mental step include a wide range of organic detergents and solvents, but
65
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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 suit-
able. 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. These and others are described more fully in
Volume III of this report series.
Brominated phenols
Three brominated phenolic compounds were once manufactured, and may
still be. Because brominated dioxins have been made in laboratory experi-
ments, they may be created during the manufacture of these compounds.
Published data describe the production method for tetra-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.
O-CRESOL TETMIROHO-0-mSOL
66
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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 fil-
tered. 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 refiltering. This step may or may not be conducted in commercial prac-
tice.
Two other brominated phenolic compounds are believed to be made by
essentially the same process. Structural formulas are as follows:
Br
2.4,6-TRIBROIIOPHENOL 2.4,6-TRIBROHO-X-CRESOl
Almost all brominations of organic compounds are low-temperature pro-
cesses because bromine is readily vaporized 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 mate-
rials, brominated dioxins likely would appear in the crude product. If the
product is recrystallized, the dioxins could be constituents of a waste
sludge.
The literature mentions dioxins that are both brominated and methylated
(See Table 3 of Volume III of this series). 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.
Q-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 p-nitrophenol.
67
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The manufacture of o-nitrophenol is a
benzene with sodium hydroxide in a process
hydrolysis method of chlorophenol production.
follows:
hydrolysis of o-nitrochloro-
essentially identical to the
The chemical reaction is as
+ NaOH
+ 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:
NaOH
NOj HO'
2NaNO2
This reaction is possible, and o-nitrophenol may be a source of dioxin
contamination. See also Volume III of the report series.
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.
68
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C02
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 unsub-
stituted 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 decom-
poses primarily into phenol and carbon dioxide, but also into smaller
amounts of phenyl salicylate, which in turn condenses to xanthone:
PHENYL SniCYUTE
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.
69
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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 (methoxy-
aminobenzene), which in several forms are important dye intermediate chemi-
cals. These might condense in appropriate environments into the dioxin
structure through loss of methyl amine. The environments would probably be
acidic:
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
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) (01ie, 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.
70
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Another team of investigators reported finding the same dioxins in
Switzerland (Buser and Bosshardt 1978). This study quantitatively deter-
mined 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 Co. reported finding ppb
levels of chlorinated dioxins in particulate 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 fire-
places, a charcoal grill, and cigarettes. See Table 12. 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. Concen-
trations 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
measureable 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. 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. 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 emis-
sions, 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.
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 6 other TCDD
isomers.
The formation of dioxins from the thermal decomposition of chloro-
phenols 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 pentachloro-
phenol did not produce the dioxin. In 1975, a series of pyrolysis experi-
ments 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,
71
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TABLE 12. DIOXINS IN SELECTED SAMPLES'
(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 parti culates
Dow rotary kiln incinerate
w/supplementary fuel
Dow rotary kiln incinerate
w/o supplementary fuel
Dow powerhouse fired with
fuel oil/coal
TCDD's
2,3,7,8-TCDD
0.3-100
0.7-2.6
Other
TCDD
isomers
0.8-18
0.5-2.3
0.03-0.04
0.005-0.03
none
none
none
r none
r 110-8200
none
none
none
none
none
1800-12,000
38
Hexa-CDD's
7-280
9-35
0.09-0.4
0.02-0.14
0.03-1.2
none
1-20
1.4-5.0
1300-65,000
2
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
2000-510,000
4
OCDD
490-20,500
650-7500
0.4-31
0.35-22
0.05-2.0
0.10-0.35
190-440
9-950
3000-810,00
24
IX)
(continued)
-------
TABLE 12 (continued)
Source
Automobiles
catalytic - carbon
catalytic - rust
noncatalytic
diesel trucks
\
Fireplaces (scrapings)
Cigarettes (tars)
Charcoal-grilled steaks
Residential electrostatic
preci pita tor
Parti culates from rotary
kiln scrubber water
w/supplemental fuel
w/o supplemental fuel
Filtered scrubber water
Cooling tower residues
Sewer waters before treat-
ment (concentration-ppt)
2,3,7,8-TCDD
none
0.4
none
3.0
0.1
none
none
0.6
4
Other
TCDD
isomers
0.1
4.0
4.0
20.0
0.27
none
none
0.40
6
2500
0.0028
1.6-6.0
1-4
Hexa-CDD's
0.5-2.0
0.7
none
4-37
0.23-3.4
4.2-8.0
none
34
200
3400
0.005
10
N^A.b
Hepta-CDD's
2-14
3
3
35-110
0.67-16
8.5-9.0
3-7
430
970
26,000
0.024
12-25
N.A.b
OCDD
8-72
28
10-16
190-280
0.89-25
18-50
5-29
1300
1200
42,000
0.026
56-119
3-1500
to
? Source: Dow Chemical, U.S.A. 1978.
N.A. = not applicable.
-------
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 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
10-5 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 chloro-
phenates, 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 character-
istics 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 contami-
nants of the wastes being burned. For example, silvex-treated grass clip-
pings, 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:
2 CH4
2,6-DIHETHUPHENOL
I.6-OIHETHVIOIBEN20-P-OIOXIN
74
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Because PRO is highly resistant to acids, bases, detergents, and hy-
drolysis 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 stan-
dards used in their studies. Some of these dioxin sources and the names of
the dioxins provided are listed in Table 13.
75
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TABLE 13. 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, D.C.,
U.S.A.
Dow Chemical, U.S.A.
Midland, Michigan
ITT Research Institute
Chicago, Illinois,
U.S.A.
A. E. Pohland
Food and Drug
Administration
Washington, D.C.,
U.S.A.
A. Poland
McArdle Laboratory for
Cancer Research
University of Wisconsin
Madison, Wisconsin,
U.S.A.
Dow Chemical, U.S.A.
Midland, Michigan
2-mono-CDD
2,3-di-CDD
2,7-di-CDD
2.8-di-CDD
2,4-tri-CDD
3,7-tri-CDD
2,3,7-tri-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-COD
1,2,3,4,6,7,8-hepta-CDD
2,3,7,8-TCDD
OCDD
MC-TCDD
Buser (1978)
Buser (1978)
Buser (1978)
Buser (1978)
Buser (1978)
Villanueva (1973)
Firestone (1977)
hexa-CDD
hepta-CDD
octa-CDD
Firestone (1977)
O'Keefe et al.
(1978)
C. D. Pfeiffer
(1978)
76
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SECTION 4
SOURCES OF HUMAN EXPOSURE
The toxicity of some dioxins, especially 2,3,7,8-TCDD, has been demon-
strated in a number of incidents of human exposure. The most serious inci-
dents, including one man-made disaster, have affected the general public;
these incidents have resulted from industrial accidents, improper disposi-
tion 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 summa-
rizes 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 (Homberger et al. 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, Panel!i, 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
77
-------
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 acci-
dent, and officials of other affected towns were not told until Monday. The
plant resumed normal operations Monday morning. No official 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. 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 7).
The most heavily contaminated area of 267 acres was designated Zone A, and
was further divided into seven numbered subzones corresponding to the rela-
tive degrees of contamination. The population of Zone A was evacuated. A
less contaminated area of 665 acres was designated Zone B; official evac-
uation 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.
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). Official-
ly, 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, Fanneli, 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,
but a thorough medical survey of the adult population was never conducted.
Since 2,3,7,8-TCDD had been shown to cause birth defects and sponta-
neous abortions in laboratory animals, the incidence of birth problems in
78
-------
N
ICMESA
Figure 7. Map of Seveso area showing zones of contamination (A and B)
and zone of respect (R).
(Source: Adapted from Panel!i, et al. 1980)
79
-------
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 spon-
taneous 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 loca-
tions, 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 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.
80
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Contained or Landfilled 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 con-
taining 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 Pharmaceu-
tical 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, as 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 landfill ing 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
kilograms of dioxins may be present in the buried wastes (Chemical Week
1978b; Dickson 1978; Chemical Week 1978c). In 1969, when dioxin contam-
inants 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).
81
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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 commu-
nity, 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 chemi-
cals 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 land-
fill found TCDD's in dust from these plants and in water samples taken from
sediments in a nearby creek (Chemical Regulation Reporter 1980).
One of the largest accumulated quantities of dioxin-contaminated anhy-
drous 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
Volume II of this report series.)
Incinerated Wastes—
A number of present and previous producers of 2,4,5-TCP and 2,4,5-T
disposed 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 dis-
carded 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 incinera-
tion by the U.S. Air Force of 10,400 metric tons of Herbicide Orange con-
taining 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).
Dow believes that the observed presence of TCDD's and other dioxins in
Midland and other metropolitan areas is due not only to chemical inciner-
ators but to various other combustion sources such as powerhouses, diesel
engines, charcoal grills, etc. (Dow Chemical Co. 1978; Rawls 1979).
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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.
Little published information addresses the question of dioxins in such
industrial water effluents. A 1978 report from Dow Chemical Co. contends
that their 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. No
dioxins were detected, however, in fish collected above the Dow effluent
outfall.
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 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 particulate matter.
In 1976, analysis of effluent water from the Vertac plant in
Jacksonville, Arkansas, showed 0.2 to 0.6 parts per billion of 2,3,7,8-TCDD
(Sidwell 1976a). In contrast, analysis of effluent from the city stabiliza-
tion ponds, to which the plant effluent was sent, showed no 2,3,7,8-TCDD
(Sidwell 1976b). Because no detection limits were reported, the presence of
2,3,7,8-TCDD 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 one hundred 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 con-
tained 8 ppb TCDD's Bottom core samples from the Vertac cooling pond con-
tained 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 contained 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
83
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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 (Salkinoya-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 trichloro-
phenol contamination and also 37 parts per billion 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 inci-
dent 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 exam-
inations 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 broad!eaf 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; pasture!ands; and food crops
such as rice and sugar cane. Regulatory and environmental actions have now
halted most of these uses of chemicals that may contain dioxins, but a
number of public health incidents have been associated with herbicide appli-
cations.
In Oregon, application of 2,4,5-T and si!vex 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 appli-
cations. 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
84
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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 appli-
cations 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 chil-
dren in South Vietnam could be assumed to have acquired hereditary defects
from this cause (Young et al. 1978). Others claim that these reports are
virtually impossible to validate. The National Academy of Sciences con-
cluded 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 et al. 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 indi-
cation 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
exposured 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 suspect (Young
et al. 1978). After an investigation, it was concluded that there was no
evidence to implicate 2,4,5-T as the cause of the deformities.
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In Australia, skin rashes, respiratory problems, and higher incidences
of birth defects and infant mortality may be associated with 2,4,5-T spray-
ings 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 applica-
tions to lawns for weed control. Until 1979, si 1 vex was also a common
constituent of many of these formulations.
There is no 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.
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 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 con-
taminated 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). Fanelli et al. (1980b) and Cocucci 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 con-
taminated 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 sub-
sequent 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 USDA 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 consumption of gelatin is estimated at 32 million kilo-
grams 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
86
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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 14.
Analysis by Dow Chemical Company of fish from the Tittabawassee River,
which receives the effluent from their Midland complex, revealed the pres-
ence of TCDD's, Hexa-CDD's, and OCDD in trace quantities (Dow Chemical
Company 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. The Food and Drug Administration has recommended
that Michigan set a maximum residue level for dioxins in fish at 100 parts
per trillion (Toxic Materials News 1979e).
TCDD's have been recently detected in leather meal, although in un-
quantified 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 Co. reported that their analysts were unable to
detect 2,3,7,8-TCDD in two surface water samples taken from the Titta-
bawassee 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
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TABLE 14. DIOXINS IN COMMERCIAL GELATIN
Sample No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Sample identity
Bulk domestic pork skin gelatin
Bulk domestic pork skin gelatin
1975 Consumer package (Texas)
1975 Consumer package (Texas)
1977 Consumer package
(Washington, O.C.)
1977 Consumer package
(Washington, D.C.)
1977 Consumer package
(Washington, D.C. )
Imported bulk gelatin
(Columbia, South America)
Imported bulk gelatin-A
(Mexico)
Imported bulk gelat"in-A
(Mexico)
Imported bulk gelatin-A
(Mexico)
Imported bulk gelatin-B
(Mexico)
Conrnercial blend (67% domestic
pork skin gelatin, 33%
Mexican-A)
Commercial blend (65% domestic
pork skin gelatin, 36%
Mexican-A)
Commerical blend (91% domestic
pork skin gelatin, 9%
Mexican-A)
~~WF, '
ppm
0.0
0.0
3.8
6.4
N.A.C
N.A.
N.A.
0.01
3.5
7.5
8.3
0.3
2.2
3.1
1.0
Oioxins, ppb
",2.4,6.7.9
HCDD
0.00
0.00
0.00
0.00
0.00
0.03
0.1
0.00
0.02,0.03
0.02,0.02
0.02,0.02
0.00,0.00
0.01,0.01
0.01,0.01
0.01,0.01
,2,3,6,7,9
HCDD
0.00
0.00
0.2
0.2
0.00
0.2
0.7
0.00
0.3,0.3
0.1,0.1
0.2,0.4
0.00,0.00
0.06,0.08
0.05,0.08
0.02,0.03
1,2,3,6,7,8
HCDD
0.00
0.00
0.00
0.00
0.00
0.03
0.4
0.00
0.4,0.6
0.3,0.2
0.6,0.8
0.00,0.00
0.2,0.3
0.1,0.2
0.04,0.09
1.2,3,7,8,9
HCDD
0.00
0.00
0.03
0.04
0.00
0.05
0.09
0.00
0.05,0.02
0.05,0.09
0.07,0.2
0.00,0.00
0.02,0.09
0.02,0.07
0.01,0.02
1,2,3,4,6,7,9
HpCDD
0.01
0.0
0.0
0.0
0.02
0.2
0.8
0.2
3.8,3.9
2.5,2.7
3.5,4.0
0.02,0.02
0.9,0.9
0.6,0.5
0.2,0.3
1,2,3,4,6,7,8
HpCDD
0.0
0.0
0.1
0.3
0.02
0.16
0.8
0.2
4.6,5.3
2.8.2.9
3.6,5.0
0.02,0.02
1.2,1.2
0.6,0.8
0.3,0.4
OCDD
0.1
0.0
0.2
0.4
0.1
0.2
0.6
0.6
20,16
20,17
21,18
0.1,0.1
4.8,4.3
2.9,1.9
1.4,1.1
Total
Dioxins
0.1
0.0
0.6
1.0
0.2
0.8
3.6
0.9
30.26
25,23
29,28
0.1,0.1
7.0,6.9
3.8,3.6
2.0,2.0
00
00
Source: Firestone 1977.
b Limits of quantitation were about 0.006, 0.012 , and 0.018 ppb for the HCDD's, HpCDD's, and OCDD respectively, using electron-capture
gas-liquid chromatography.
c N.A. = Not analyzed.
-------
direct chlorination (Gilman 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 environ-
ment.
Miscellaneous Pesticide Uses
In addition to their principal uses as a raw material and an agricul-
tural 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. Environmental Protection Agency 1978i). These are used
on surfaces of 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. Envi-
ronmental 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.
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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 hexa-
chlorophene and also required that these drugs be made available only by
prescription. Products containing 0.1 percent hexachlorophene as a preser-
vative 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 refer-
ences 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 hexa-
chlorophene (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 preg-
nancy; 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.
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 manu-
facturing 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 occupa-
tional). 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 expo-
sure 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
90
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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 mortal-
ity 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 connec-
tion 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 Asso-
ciation Journal 1980). The following paragraphs represent only a sampling
of these incidents, most of which involve the manufacture of 2,4,5-TCP.
Table 15 summarizes some of the other incidents not described in detail.
Table 16 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. Prelim-
inary 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 exhaust 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).
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).
91
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TABLE 15. REPORTED INCIDENTS OF OCCUPATIONAL EXPOSURE TO DIOXINS
DURING ROUTINE CHEMICAL MANUFACTURING
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
Manufacturer/plant location
N.A. /Nordrhein, Westfallen
N.A./N.A.
Boehringer/N.A.
Boehringer, Ingelheim/Hamburg
Diamond Alkali /Newark, New Jersey
Hooker/N.A.c
Diamond Shamrock/N.A.c
N.A./N.A.
Dow Chemical /Midi and, Michigan
Spolana/N.A.
N.A./N.A.
N.A./N.A.
Linz Nitrogen Works/N.A.
Bayer/Uerdingen
Thompson Hayward/Kansas City, Mo.
Chemical
produced
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
Number of
persons exposed
17
60
37
31
29
N.A.
N.A.
128
60
78
25
1
50
5
N.A.
PO
, Adapted from Young et al. 1978.
N.A. - Not available.
Not known whether occupational exposure was involved in the incident.
-------
TABLE 16. OCCUPATIONAL EXPOSURES TO DIOXINS THROUGH ACCIDENTS IN
THE CHEMICAL MANUFACTURING INDUSTRY
Year
1949
1953
1956
1962
1963
1966
1968
1976
Country
United States
West Germany
France
Italy
Netherlands
France
United Kingdom
Italy
Manufacturer/location
Monsanto/Nitro, West Virginia
BSAF/Ludwigshafer
Rhone Poulene/Grenoble
Phi 1 ips-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
1C
CO
. Adapted from Young et al. 1978.
These were not workers but local residents (124 children and 10 adults); no workers were reported
affected.
-------
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 associ-
ated 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 Sal a 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, apparently 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 popular 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 trans-
portation 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 17 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
94
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TABLE 17. INDUSTRIES USING DIOXIN-RELATED CHEMICALS
Industry
Chemical(s)
Process application
en
Textiles
Leather tanning
Wood preserving
Pulp and paper
Pesticide formulators
and applicators
Automotive
Miscellaneous industries
Household and industrial
cleaning products
Building/construction
Drug and cosmetics
Paint
Farming (cattle)
Railroad, telephone,
(construction and
maintenance)
TCP
TCP, PCP
PCP
TCP, PCP
2,4,5-T
2,4-D
si 1 vex
ronnel
erbon
hexachlorophene
TCP
TCP
TCP,
hexachlorophene
PCP
hexachlorophene
TCP, PCP
2,4,5,-T, 2,4-D
2,4,5-T
si 1 vex
2,4-D
Process water fungicide
Process water fungicides
Active ingredient in dip vat/pressure treatment
Process water slimicide, fungicide
Active ingredient formulated or sprayed
Active ingredient formulated or sprayed
Active ingredient formulated or sprayed
Active ingredient formulated or sprayed
Active ingredient formulated or sprayed
Active ingredient formulated or sprayed
Metal cutting fluids, foundry core washes
Slimicide in cooling tower waters
Active ingredient disinfectant
Termite control
Product preservative or active ingredient
Preservati ve/mi1dewci de
Rangeland weed control
Weed control on rights-of-way
-------
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 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 Volume II of this series).
People involved in the application of herbicides manufactured from or
formulated with 2,4,5-TCP and derivatives may be exposed to dioxin contam-
inants. 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 con-
flict 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 (GAO) 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, 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 (Severe 1979).
Chemical Laboratories
In 1957, a research worker in a laboratory synthesized the 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 hospi-
talized (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 scien-
tists had been working on the synthesis of dioxin standards. They had
performed the synthesis under a fume hood and had worn overalls and dispos-
96
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able 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 devel-
oped a set of elaborate laboratory safety rules to be used when working with
dioxins.
Similarly, stringent procedures are exercised by independent labora-
tories who analyze samples containing dioxins. The Brehm Laboratory of
Wright State University, Dayton, Ohio, includes a specially equipped labora-
tory 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).
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 a con-
tract waste disposal firm. 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, penta-
chlorophenol, or hexachlorophene (U.S. Environmental Protection Agency
1978dJ. Also being sampled is a wood-preservation operation in which penta-
chlorophenol 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 dioxins 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 quantified) of hexa-CDD's and
hepta-CDD's were found in the soil in the vicinity of the product storage
area.
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SECTION 5
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. Subsec-
tions 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 biodegradabilityt 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.
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.
Biodegradation: the molecular degradation of an organic substance re-
sulting from the complex actions of living organisms. A substance is said
to be biodegraded to an environmentally acceptable extent when environ-
mentally 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 bio-
degradation.
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Ward and Matsumura studied the biodegradation of 14C-label led 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 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 coworkers studied two types of soil, which were incubated
with 2,3,7,8-TCDD at concentrations of 1, 10, and 100 ppm and with 14C-
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 14C-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 loamy sand, 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 14C02 as an indication of
microbial degradation of the labeled dioxins.
Very little C02 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 metabo-
lites were found in TCDD-treated soil after 1 year. About 5 percent of the
14C-2,7-DCDD had degraded to liberate 14C02 after 10 weeks. Concentrations
of 14C-2,7-DCDD in the soil had a slight effect on 14C02 evolution. It was
postulated that the decrease in C02 liberation at the highest level may have
resulted from the toxicity of the DCDD isomer to the microbes at this con-
centration. Evolution of 14C02 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 14C02" 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 ana-
lyzed for both the herbicide and 2,3,7,8-TCDD. Results are presented in
Table 18.
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TABLE 18. CONCENTRATIONS OF HERBICIDE ORANGE
IN THREE TREATED TEST PLOTS1
AND 2,3,7,8-TCDD
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,
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
2.5
c
0.255
c
c
c
0.042
0.375
0.250
0.075
0.046
c
c
, Plots treated with 4480 kg herbicide per hectare.
Composite sample from upper 0 to 15 cm layer of soil.
Not analyzed.
100
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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 semi logarithmic plots of
dioxin concentrations in soil against days after incorporation of the diox-
in, they concluded: (1) that there was no evidence that the rate of degra-
dation 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 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 19.
TABLE 19. DEGRADATION OF 2,3,7,8-TCDD IN SOIL3
(parts per trillion 2,3,7,8-TCDD)
Controls
Outdoor exposure
Tilled (top layer)
Untilled
Greenhouse
Tilled (top layer)
Untilled
Length of exposure, weeks
0
1100 - 1300
9
1100
1000
640
810
23
520
530
460
530
Source: Bartleson, Harrison, and Morgan 1975.
101
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The investigators concluded that the accelerated rate of degradation
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. Reduc-
tion 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 break-
down. 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 con-
cluded 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 des-
cribed results of Matsumura and Benezet in 1973) or enriched by the addition
of organic nutrients. No positive degradation effects have been found.
Investigators from the Microbiological Institute in Zurick,
Switzerland, have found that microbes cannot contribute quickly or effi-
ciently 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 coworkers 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.
H H
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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 energy, usually in a specific wavelength range. In photodegrada-
tion 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 mecha-
nisms 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 photolytical-
ly 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 the basic dioxin structure remains.
When penta-CDD is photodegraded, it may go to a TCDD isomer. (For further
discussion see pp. 138-139 of Section 6.)
Several dioxin photodegradation studies are discussed in the paragraphs
that follow. Major findings from these studies are summarized in Tables 20
and 21.
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
103
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TABLE 20. PHOTODEGRADATION OF 2,3,7,8-TCDD
o
-p*
Physical conditions
TCDD in methanol
TCOO in methanol
TCDD (crystalline)
in water
TCOD on soil
TCDD in benzene/water/
surfactant
TCDD crystals on glass
plate
TCDD in isooctane and
1-octanol
TCDD in Herbicide
Orange, on glass
TCDD in commercial
Esteron herbicide,
on glass
TCDD in Esteron base,
on glass
Light
source
Artificial
(100 jjw/cm2)
Natural
sunlight
Artificial
(sun lamp)
Artificial
(•sun lamp)
Natural
sunlight
Artificial
(G.E. RS
sunlamp)
Natural
sunlight
Natural
sunlight
Natural
sunlight
Length of
exposure
24 h
7 h
NR
96 h
NR
14 days
40 min
24 h
6 h
6 h
2 h
Amount
degraded, %
100
100
0
0
>0
0
50
100
60
70
90
Reaction
products
Trichlorodibenzo-p-dioxin,
Dichlorobenzo-p-dioxin
NRa
NAb
NR
NR
NR
NR
NR
Reference
Crosby et al .
1971
Crosby et al.
1971
Crosby et al.
1973
Plimmer et al.
1973
Crosby et al.
1971
Stehl et al.
1973
Stehl et al.
1973
Crosby and Wong
1977
Crosby and Wong
1977
Crosby and Wong
1977
" NR = Not reported.
0 NA = Not applicable.
(continued)
-------
TABLE 20 (continued)
o
en
Physical conditions
TCDD in Herbicide
Orange, on plant
leaves
TCDD in Herbic.ide
Orange, on soil
TCDD on silica gel
TCDD on silica gel
TCDD in Seveso soil
with ethyl oleate-
xylene mixture
TCDD in 1-hexadecyl-
pyridinium chloride
(CPC)
TCDD in sodium dodecyl
sulfate (SDS)
TCDD in methanol
TCDD in Seveso soil/
treated with aqueous
olive oil solution or
olive oil/cyclohexanone
TCDD in emulsif iable
si 1 vex formulation
TCDD in granular
si 1 vex formulation
Light
source
Sunlight
Sunlight
Artificial A
>290 nm
Artificial A
= 230 nm
Sunlight ar-
tificial
(Phillips MLU
300 W)
Artificial
Artificial
Artificial
t' tural
sunlight
Natural
sunlight
Natural
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
9 days
=6 days
rl3.5 days
sunlight 1
Amount
degraded, %
100
70
10
92
98
>90
100
>90
=50
=100
=50
=75
>90
50
50
Reaction
products
NRa
NR
NR
NR
NR
NR
NR
NR
NR
NR
NRa
Reference
Crosby and Wong
1977
Crosby and Wong
1977
Gabefuigi
1977
Gabefuigi
1977
Bertoni
1978
Botre et al.
1978
Botre et al.
1978
Botre et al.
1978
Crosby
1978
Nash and Bealle
1978
Nash and Bealle
1978
* NR = Not reported.
0 NA = Not applicable.
-------
TABLE 21. 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
OCDD in methanol
DCDD in isooctane and
1-octanol
Light
source
Artificial
UV light 100
MW/cm2
Artificial
sunl ight
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 win
Amount
degraded, %
>20
lore rapid in
natural sunlight
;han artificial
UV light
66
20
70
90
20
6
?70
50
Reaction
products
Series of chlorinated
dioxins 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 1976
Buser 1976
Stehl et al.
1973
Stehl et al.
1973
Crosby et al.
1971
Stehl et al.
1973
NR = Not reported.
-------
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
decomposed 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. Pre-
liminary 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 difficul-
ties. Irradiation apparently had no effect on the water suspension. A
crystalline state may prohibit the loss of chlorine or obstraction of hydro-
gen 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).
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 expo-
sure, 30 percent of the OCDD remained unchanged; the major reaction products
were hexa- and hepta-CDD's and trace amounts of penta-CDD's. After 24 hours
of irradiation, the hexa- and hepta-CDD's still constituted the major reac-
tion 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 poly-
chlorinated dioxins could have environmental significance.
Exposure of TCDD's and DCDD's in iso-octane 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). Anal-
ysis 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.
107
-------
When a solution of OCDD and iso-octane was exposed to artificial sun-
light, about 80 percent of the OCDD remained unreacted after 18 hours. With
a solution of OCCD 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 6.7 mg/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 concentra-
tion of the dioxin was reduced by 92 percent after 7 days. When irradiation
was done with light of shorter wavelength (>230 nm), the dioxin concentra-
tion 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).
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 the 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.
108
-------
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 con-
taminated soil samples were used for standards. In the pure dioxin solubil-
ization 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), an anionic surfactant, 1-hexadecylpyridinium sorbitan
monooleate (Tween 80), hexadecyltrimethylammonium bromide, and 1-hexadecyl-
pyridinium chloride (CPC).
Results showed that CPC was the best solubilizing agent for contam-
inated soil taken from the Seveso area, whereas in the pure dioxin experi-
ment 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 si 1 vex formula-
tions 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 emulsifi-
109
-------
able 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. 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-dichlorphenoxyacetic 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 is 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 en-
hanced 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).
110
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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 Eg!in Air Force Base in Florida (Commoner and Scott 1976). A
map of this area is shown in Figure 8. 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-inch-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 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 occurred.
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 inches of the soil layer.
From March 1974 to February 1975 the Air Force performed another study
at the Eg!in 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:
Depth, in. Concentration, ppt
0-1 150
1-2 160
2-4 700
4-6 44
111
-------
INSTRUMENTED 1 SQUARE
MILE TEST GRID
LEGEND
» CONTRAVES
* INACTIVE ASKANIA
5 SPOTTING TOWER
) CONTROL BLDG.
- PAVED RO..
= CLAY ROAD
== SAND ROAD
TOWER
— INTERANGE BOUNDARY LINE
• RANGE GATE AND BARBED
WIRE FENCE
O
Figure 8. Map of Test Area C-52A, Eglin Air Force Base Reservation, Florida
(Source: Young, Thai ken, and Ward 1975).
-------
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 22 presents analytical results of plot sampling 4 years
after, application of Herbicide Orange at various rates. Table 23 gives
results of a similar test performed at Eglin Air Force Base in Florida.
In the tests reported in Tables 22 and 23, 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 inches 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 earlier on p. Ill) had surface 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 contaminat-
ed areas at Seveso showed that the dioxin penetrated to a depth of 10 to 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 sugges-
tion 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
113
-------
TABLE 22. CONCENTRATIONS OF 2,3,7,8-TCDD AT UTAH
TEST RANGE 4 YEARS AFTER HERBICIDE ORANGE APPLICATIONS'
(ppt)
Soil depth, in.
0-6
6-12
12-18
Rate of Herbicide Orange application, Ib/acre
1000
650
11
NAb
2000
1600
90
NA
4000
6600
200
14
? Source: Young et al. 1978.
D NA = Not analyzed.
TABLE 23. CONCENTRATIONS OF 2,3,7,8-TCDD AT EGLIN AIR FORCE BASE
414 DAYS AFTER HERBICIDE ORANGE APPLICATION3
Soil depth, in.
0-6
6-12
12-18
18-24
24-30
30-36
Herbicide Orange, ppm
1866
263
290
95
160
20
2,3,7,8-TCDD
concentration in soil,
250
50
<25b
<25b
<25b
<25b
ppt
j~ Source: Young et al. 1976.
Detection limit.
114
-------
soil was removed and replaced with fresh soil. After removal and replace-
ment of the 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 microagro-
ecosystem is shown in Figure 9. Two commercially available silvex formu-
lations, one granular and one emulsifiable, were tested. The test and
control formulations were applied three times to turf in five microagroeco-
systems and once to turf on the outdoor plots. Throughout the test period a
sprinkler system applied water to the soils to simulate rainfall.
The 2,3,7,8-TCDD used in the study was labeled with radioactive hydro-
gen or 3H. Throughout the study the labeled dioxin (or breakdown product)
was tracked by extremely sensitive radiochemical assay methods. The pres-
ence of the dioxin molecule in samples was confirmed by gas-liquid chroma-
tography.
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 microagro-
ecosystems following the first two herbicide applications showed no detect-
able 2,3,7,8-TCDD (limits of detection were 10"16 g/g*). The dioxin was
detected later, however, following the third herbicide application, and
maximum concentrations of 0.05 to 0.06 ppb were found in the leachate sam-
ples taken 7 weeks after that third application.
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 for dioxins 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
ID*16 g/g may also be expressed as 0.1 fg/g (0.1 femtogram per gram).
It is equivalent to 0.0001 ppt.
115
-------
INLET FILTER
HOLDER
PLATE GLASS (1 cm)
REMOVABLE ACCESS PANELS
PLASTIC(0.7 cm)
OUTLET FILTER
HOLDER
Figure 9. Diagram of microagroecosystem chamber.
116
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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, Morris, and Hawkes 1973).
The transport of dioxin-contaminated soil into lakes or streams by
erosion constitutes another possible route of contamination. This is evi-
denced 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 concen-
trations 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 indi-
cated 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 combina-
tion 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 con-
centrations 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 chloro-
phenol 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 have migrated
from process waste containers in the landfill of a former 2,4,5-T production
117
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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 mussels and
fish (Richards 1979; Fadiman 1979; Cincinnati Enquirer 1979; Tiernan et al.
1980). TCDD's apparently are also being leached into surface and ground-
waters 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 15 g) 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 micro-
agroecosystems. 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 formu-
lations containing the dioxin are used.
Results of other investigations indicate that water-mediated evapora-
tion 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; 01 ie,
Vermuelen, and Hutzinger 1977; Buser and Rappe 1978; Dow Chemical Co. 1978;
Tiernan and Taylor 1980). A recent report of Dow Chemical (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 chloro-
phenol 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
disasterous consequences.
The ability for a chemical to accumulate and to become concentrated or
participate in biomagnification depends primarily on its availability to
118
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organisms, its affinity for biological tissues, and its resistance to break-
down and degradation in the organism.
Bioaccumulation, Bioconcentration, and Biomagnification in Animals
The biological activity of dioxins with respect to accumulation, con-
centration, 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 accumu-
lated in biological segments of the environment. The increase of pollutant
concentrations in the tissues of organisms at successively higher trophic
levels is biomagnification.
Several investigators (Panel!i 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 24 indicate that TCDD's
accumulate in environmentally exposed wildlife.
to contain TCDD's at whole-body concentrations
All field mice were found
ranging from 0.07 to 49 ppb
from an area where the soil
12 ppb (mean value 3.5 ppb).
(mean value 4.5 ppb). The mice were collected
contamination (upper 7 cm) varied from 0.01 to
These data are in agreement with Air Force studies by.Young et al. (des-
cribed below), which indicate that rodents living on dioxin-contaminated
land concentrate TCDD'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 24. TCDD LEVELS IN WILDLIFE3
Animal
Field mouse
Hare
Toad
Snake
Earthworm
No. of samples
analyzed
14
5
1
1
2b
Tissue
Whole body
Liver
Whole body
Liver,
adipose tissue
Whole body
Positive
14/14
3/5
1/1
1/1
1/2
TCDD level,
ng/g (ppb)
Average
4.5
7.7
0.2
2.7
16
12
Range
0.07-49
2.7-13
j* Source: Fanelli et al. 1980.
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
119
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the defoliation program in Southeast Asia. The studies took place at the
test site at Eglin Air Force Base in Florida (Figure 8) 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 terato-
genic 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, Thai ken, 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 inches of soil, it was thought that a food source might be respon-
sible 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 (ranging from <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 the average value for TCDD's in the soil
of Grid 1, which was 339 ppt. They concluded that biomagnification was evi-
denced by the significantly higher level? of TCDD's in mouse liver than in
soil.
120
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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 cap-
tured in TA C-52A. Specimens captured at a control site showed concentra-
tions 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, Thai kin, 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. All
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 C-52A 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 solubil-
ity 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 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, meadow!ark, dove, opos-
sum, 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, opossum, or grass-
hopper. 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.
121
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It should also be noted that the composite insect sample most likely in-
cluded 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 C02. 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, con-
sisting 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 and drank from ponds that had received applications of 2,4,5-T
(Getzendance, Mahle, and Higgins 1977). Sample collection ranged from 5
days to 48 months after application; 14 samples were collected within 1 year
122
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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 (Panelli et al. 1980). The
samples were analyzed for TCDD's by GC-MS methods. Results are given in
Table 25. Figure 10 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). 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 coworkers could find no evidence that TCDD's are biocon-
centrated 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 con-
tamination was found in 103 samples of human milk collected in western
states (Chemical 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 bioaccu-
mulation 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
123
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TABLE 25. TCDD LEVELS IN MILK SAMPLES COLLECTED NEAR SEVESO
IK JULY-AUGUST 1976*
Map ,
number
1
2
3
4
5
6
7
8
9
10
Date of
collection
7/28
7/28
8/2
8/10
7/28
8/2
8/10
8/10
7/29
7/29
8/3
8/3
7/27
8/3
8/5
TCDD concentration,
ng/liter (ppt)
76
7919
5128
2483
469
1593
496
1000
116
59
80
94
180
75
<40
Source: Panel!i et al 1980.
Locations shown in Figure 10.
124
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ICMESA
N
.6
Figure 10. 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)
125
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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 be-
cause 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 liters 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 analyzed. 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. Bioaccumulations 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 mosqui-
to 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 aquat-
ic 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.).
126
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Isensee and Jones (1975) performed three experiments using algae,
duckweed, snails, mosquito fish, daphnia, channel catfish and other
organisms. Radiolabeled dioxin (14C-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 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 exper-
iment the concentrations of 14C-TCDD in the water and in the organisms were
determined and the concentration factors calculated. Table 26 summarizes
soil application rates in each experiment and type of soil used.
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 14OTCDD 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 rela-
tively high (as compared with those observed with other pesticides), espe-
cially 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).
Dow Chemical Company, a producer of pentachlorophenol and the major
producer of 2,4,5-trichlorophenol, 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 Titta-
bawassee River and tributaries. The analyses showed levels of TCDD's
127
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TABLE 26. SOIL APPLICATION RATES AND REPLICATIONS5
Total 14C-TCDD
added per tank,
M9
149
0
63
63
63
63
0
10
1
0.1
0.01
0
Type of soil and amount
of 14C-TCDD added, g
Experiment I
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 14C-TCDDc
in soil , ppm
7.45
0
3.17
0.53
0.29
0.15
0
0.1
0.01
0.001
0.0001
0
No. of
replicates
3
1
2
2
2
2
2
2
2
2
2
2
Isensee and Jones 1975.
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.
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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 collected 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.
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, if any, 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
14C-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 pg/kg levels. Concentrations
in the leaves were 3 to 5 times higher than in the fruits, which had the
lowest concentrations. 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 photodegrada-
tion. The latter possibility would agree with the photolysis results
reported by Crosby and Wong in 1977.
Cocucci and coworkers also examined specimens of garden plants such as
the carrot, potato, onion, and narcissus. Again, ug/kg levels of TCDD's
were found. In all plants, the new aerial portions appeared to contain less
dioxin than the 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
129
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plant parts. The authors again suggested that the relatively low concentra-
tions in the aerial parts of these garden plants was 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 14C-TCDD by Sorghum vulgave plants. After placing Herbicide
Orange containing 14 ppm 14C-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 col-
lection of the C02. Analysis before extraction showed a concentration of
about 430 ppt 14C-TCDD in the plant tissue. After hexane extraction, the
concentration of 14OTCDD in the plant tissue was reported as being not
significantly reduced. Young et al. concluded that the relatively high 14C
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 6
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 land-
fill. 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 contam-
inated 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-contaim'ng 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 to 3500 barrels of TCP wastes are buried or stored on the manufac-
turing site (Fadiman 1979; Cincinnati Enquirer 1979). Many of these barrels
are now leaking and contaminating nearby water bodies (Richards 1979a;
Tiernan et al. 1980).
131
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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 byproducts 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 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
(Wilkenson, 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.; Wilkenson 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). These data were obtained with a
quartz tube apparatus. Using differential thermal analysis two other exper-
imenters have observed that complete destruction occurs between 800° and
1000°C (Kearney et al. 1973b), which agrees with the work of Langer et al.
132
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(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 TCOD may be formed from precursor material (Rappe 1978).
Incineration is now used to dispose of wastes from pesticide manufac-
ture 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 is 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 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 ug/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.
133
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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/h incinerators capable of burning a
10,000-ton load of waste on a week's cruise. 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-contami-
nated debris would take years. Furthermore, 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 decompo-
sition 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, Kelso, and Hopkins 1978). It has potential applica-
tion to the destruction of pesticides and hazardous wastes. A schematic of
the process is given in Figure 11. A difficulty with developing this system
for full-scale practice may be in locating suitable materials of construc-
tion.
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 appli-
cation 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 chlo-
rinated 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.
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STACK
i
OFF-GAS
CLEANUP
WASTE
1
CO
tn
WASTE
TREATMENT
AND FEED
AIR-
WASTE AND AIR
, H20,
MOLTEN SALT
FURNACE
SALT RECYCLE
.1.
SPENT MELT
REPROCESSING
OPTION
SPENT MELT
DISPOSAL
ASH
Figure 11. Schematic of molten salt combustion process. (Source: Wilkinson, Kelso,
and Hopkins 1978, as adapted from Atomics International 1975.)
-------
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
EPA (Bailen and Hertzler 1976). A schematic diagram of these units is shown
in Figure 12. Tests have been conducted with a variety of toxic materials,
including two commercial PCB's, Aroclor 1242, and Aroclor 1254. The labora-
tory-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 matrial 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 dis-
posal 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 adsorp-
tion were conducted before the Air Force decided to incinerate Herbicide
Orange (Whiteside 1977; Young et al. 1978). Although the reprocessing
136
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PESTICIDE
DROPPING
FUNNEL
MICROWAVE
POWER SOURCE
MICROWAVE
APPLICATOR
^
TUNING
UNIT
MICROWAVE
POWER SOURCE
RECEIVER
PLASMA
REACTOR
TUBE
MASS
SPECTROMETER
6> 0
[
FLOW METERS
°2 ALTERNATE
SUPPLY GAS SUPPLY
3-WAY STOPCOCK
MANOMETER
COLD TRAP
s
VACUUM PUMP
THROTTLE
VALVE
COLD TRAP
Figure 12. Schematic of microwave plasma system
(Source: Wilkinson, Kelso, and Hopkins 1978, as adapted from
Bail en and Hertzler 1976).
137
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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-contami-
nated 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 regen-
erated. 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 (Model 1,
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 (Model 1,
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 interaction 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 (Teirnan et al. 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 5.
138
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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
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. Laboratory studies have shown, how-
ever, that light does not destroy the structure of dioxins. Under appro-
priate conditions, light converts the more toxic dioxins to less toxic forms
by removing halogen substituents (Crosby 1971). Any applications of this
principle will therefore be limited to decontamination and partial degrada-
tion, rather than to complete disposal.
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 (ppm) and irradiated the solutions at 106 rads/h (Chemical Week
1977; Panel!i 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, Kimbrough, 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
139
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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,
costs would be prohibitive for routine use of this method in waste treat-
ment.
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).
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 tech-
nique, 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 13. 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 chloriodides (Botre, Memoli, and
Alhaique 1979). The compounds are formulated in micellar solutions with
surfactants that increase the water solubility of the substances. The two
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MIXER
EXHAUST GAS
UV LIGHT
SPARGED
BATCH
REACTOR
L
J
IMPELLER
11 i i
TEMPERATURE
CONTROL
pH MONITORING
AND SAMPLING
2% Kl
SOLUTION
VENT
OZONE
GENERATOR
POWER
OXYGEN OR AIR
and
Figure 13.
irradiation
Hopkins 1978,
Schematic for ozonation/ultraviolet
apparatus (Source: Wilkinson, Kelso,
as adapted from Mauk, Prengle, and Payne 1976).
141
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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 cetylpyri-
dinium 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 addi-
tional 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 con-
taining one to three carbon atoms into perch!oroethylene, 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 dichloride in a fluid bed catalyst reactor. The
process usually creates small amounts of hexachlorobenzene, hexachloro-
ethane, 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.
142
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In cooperation with the U.S. Department of Agriculture, the Diamond
Shamrock Company 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 tech-
niques 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 chlor-
ine 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 pro-
cess 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 experi-
ment 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 tempera-
ture 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, parti-
cularly 2,3,7,8-TCDD, to microbial decomposition. Most of the studies have
concerned decomposition in the uncontrolled environment, as described in
Section 4. 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.
143
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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 char-
coal 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 became
mutated to a strain that rejected the 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 biologi-
cal/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 Co. 1978). A 2-year program of analysis of grab and composite
samples taken from the tertiary effluent stream revealed only one with a
144
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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. 83) 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 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 waste-
waters 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 bacteri-
ferous water, mud, or bark residue from water bodies polluted by chlorinated
and unchlorinated phenols and aromatic carboxylic acids, then feeding pollu-
tants 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.
Mi cropit 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 14, consists of a partially buried poly-
ethylene garbage can filled with layers of rock and soil, and flooded with
water. The study, sponsored by the U.S. EPA, 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.
145
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GROUND LEVEL
ROCK
GALVANIZED
METAL SLEEVE
212 LITER
POLYETHLENE
BARREL
55.2 cm
(1.8 ft)
GALVANIZED
BASKET
29.2 cm (11.5 in.)
20.3 cm (8 in.)
35.6 cm (14 in.)
PERFORATED
CLAY TILE
Figure 14. Internal view of pesticide micropit
(Source: Rogers and Allen 1978).
146
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SECTION 7
HEALTH EFFECTS
INTRODUCTION
On a molecular basis 2,3,7,8-TCDD is perhaps the most poisonous
synthetic chemical. As shown in Table 27, only bacterial exotoxins are more
potent poisons. Not only is this TCCD 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 (invol-
untary rapid movement of the eyeball), and liver dysfunction as manifested
by hepatomegay (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-TCCD 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 ug (10 ng) of 2,3,7,8-TCDD is the dosage expected to
result in "incipient carcinogenicity." Additionally, daily human exposure
to 4 ug 2,3,7,8-TCDD would be expected to result in a shortened lifespan,
and daily exposure to 290 ug 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 toxicologically than chlorine,
which is more active than fluorine.
At least one hydrogen atom must remain on the dibenzo-para-dioxin
nucleus.
147
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TABLE 27. TOXICITIES OF SELECTED POISONS0
Substance
Botulinum toxin A
Tetanus toxin
Diphtheria toxin
2,3,7,8-TCDDb
Sax it ox in
Tetrodotoxin
Bufotoxin
Curare
Strychnine
Muscarin
Di i sopropyl f 1 uorophosphate
Sodium cyanide
Molecular
weight
9 x 105
1 x 10s
7.2 x TO4
322
372
319
757
696
334
210
184
49
Minimum
lethal dose,
moles/kg
3.3 x 10~17
1 x 10"15
4.2 x 10"12
3.1 x 10"9
2.4 x 10"8
2.5 x 10"8
5.2 x 10"7
7.2 x 10"7
1.5 x 10"6
5.2 x 10"6
1.6 x 10"5
2.0 x 10~4
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 intraperitoneal route
.in mice.
LD50* upon oral administration in the guinea pig.
Intravenous injection in the cat.
- the dosage lethal to half of a group of test animals,
148
-------
Another finding is that the ability for a dioxin to induce* various
enzymes correlates with its toxicity, as illustrated in Tables 28 and 29.
As these tables show, 2,3,7,8-TBDD and Hexa-CDD are the only dibenzo-para-
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.
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-para-dioxin is rapidly converted by the
microsome-NADPH 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 bf 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
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 (jg 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 (Mam's 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
* An induced enzyme is one that is synthesized only in response to the
presence of a certain substrate or substrates.
149
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TABLE 28. BIOLOGICAL PROPERTIES OF DIOXINS'
Compounds
2,3,7,8-TCDD
Unsubstituted dioxiri
2,7-DCDD
2,3-DCDD
2,3,7-tri-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
Uso (rat),
mg/kg
0.04
>1000
-2000
>1000
>1000
>1000
>1000
>100
< 1
-100
-2000
Chloracne
aptitude
+++
0
0
0
0
0
-m-
+
0
Teratogenic
effect
-M-+
0
±
0
0
0
++
+
Eabryo toxic
effect
-I-M-
0
±
0
0
0
-M-
+
Source: Saint-Ruf 1978.
TABLE 29. ENZYME INDUCTION3
Compounds
2,3,7,8-TCDD
ALASb
(chick embryo)
+-M-
Unsubstituted dioxin
2,3-DCDD
2,7-DCDD
2,8-DCDD
1,3-DCDD
2,3,7-tri-CDD
2,3,7-tri-BDD
1,2,3,4-TCDD
1,3,6,8-TCDD
2,3,7,8-TBDD
Hexa-CDD
OCDD
0
0
0
0
-M-
-M-
0
+
AHHC
(chick embryo)
1
0
0
0
0
0.02
0.6
0
0.2
1.0
0.8
0
Zoxazolanine
hydroxylase
(rat)
-m-
0
-m-
0
Source: Saint-Ruf 1978.
Anino-levulinic Acid Synthetase.
Aryl Hydrocarbon Hydroxylase.
150
-------
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. Finally, phlebotomy may prove
clinically useful in treating 2,3,7,8-TCDD intoxication.
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 one-compartment open model. Table 30 shows the body burden
of 14C-2,3,7,8-TCDD in rats given a single oral dose of 1.0 M9/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 15, 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 14C-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 = Css (l-e-kt)
where C. = the concentration of 14C activity in the liver at time t
C = the concentration of 14C activity in the liver at steady state
sl = elimination rate constant from the liver
Values of C equal to 0.25 pg equivalent 2,3,7,8-TCDD per gram of liver per
\jg dose, ar?(f 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 l/12th to l/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 C and k equal _£o
0.058 (jg equivalent TCDD per gram of fat per |jg dose Sand 0.029 day ,
respectively.
151
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TABLE 30. 14C BODY BURDEN ACTIVITY IN SIX RATS
GIVEN A SINGLE ORAL DOSE OF 1.0 ug OF 14C-2,3,7,8-TCDD/kga
Sex
Male
Male
Male
Female
Female
Female
Mean ± SD
f
0.66
0.77
0.91
0.93
0.87
0.91
0.84 ±0.11
_i
k, days
0.026 ±0.001b
0.018 ±0.001
0.021 ±0.000
0.022 ±0.001
0.019 ±0.001
0.033 ±0.002
0.023 ±0.006
t^, days
27
39
33
32
36
21
31 ±6
Source: Rose et al. 1976. Rose gives the following equation:
-kt
Body burden = f (dose)e
where f is the fraction of the dose absorbed; k, the elimination rate
constant; tt , the body burden half-life.
Confidence limits 95%.
152
-------
25
to
o
o
o
ce
20
15
10
NOTE:
EACH POINT REPRESENTS
THE MEAN + SE FOR
THREE RATS.
14
Figure 15. Excretion of C activity by rats following
a single oral dose of 50 yg/kg (0.14 yCi/kg) 2,3,7,8-TCDD.
(Source: Piper, Rose and Gehring 1973)
153
-------
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 14C-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 administred 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 administration, approximately 50 percent of the
body burden of OCDD was found in the liver; over 95 percent of the radio-
activity 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.
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 approxi-
mately 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
154
-------
the Ah locus must involve a minimum of three gene products at each of two
nonlinked loci, plus a structural gene for cytochrome Pi-450 (P-448) as
well. Other investigators have demonstrated that cytosolic binding sites
for 2,3,7,8-TCDD enhance AHH activity by de novo* protein synthesis of
apocytochrome P-448, and that these binding sites are not necessarily asso-
ciated with AHH inducibility regulated by the Ah locus (Guenthner and Nebert
1977; Kitchin and 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 16 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 Pi-450.
Other 2,3,7,8-TCDD molecules can then react with newly formed cytochrome
Pi-450, 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 suscep-
tible 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,
6-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);
Glutathione S-transferase (Mam's 1979);
Ethoxycoumarin deethylase (Parkki and Aitio 1978).
Marselos et al. (1978) found that 2,3,7,8-TCDD decreases activity of
the following enzymes:
primary or of recent onset
155
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Ul
LIVING CELL
NUCLEUS
UNKNOWN SITE
IN NUCLEUS
2,3,7,8-TCDD
INDUCER-RECEPTOR
RECEPTOR COMPLEX MOVES
IN CELL INTO NUCLEUS
!-450 GOES INTO MEMBRANE
REACTS WITH POLLUTANTS
._
MESSAGE NOW
"RECEIVED"
RESPONSE IS SYNTHESIS OF
SPECIFIC MESSENGER RNA'S
INNOCUOUS
PRODUCTS
EXCRETED
mRNA'S DIRECT SYNTHESIS
OF SPECIFIC PROTEINS
REACTIVE
(CYTOCHROME
INTERMEDIATE
REACTIVE INTERMEDIATE
BINDS CRITICAL TARGET
CRITICAL TARGET
IN OTHER CELLS
DRUG TOXICITY OR
INITIATION OF CANCER
Figure 16. Proposed mechanism for induction of AHH and toxicity by 2,3,7,8-TCDD
(adapted from Fox 1979).
-------
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-TCDD 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 17) 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 abnormal-
ities in lipid metabolism and liver function. In this study, the levels of
triglycerides and y-glutamyl transpeptidase (GGT)t were elevated in five men
and were
* Bronze colored (wear and tear) pigments.
t Liver enzyme.
157
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- r*.
LIPID
DROPLET
Figure 17. Schematic of rat liver 13 days after
administration of 2,3,7,8-TCDD (50 yg/kg). Note
concentric membrane array surrounding lipid
droplet. X20502.
(Source: Redrawn from Albro 1978)
158
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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 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.
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
post-mortem 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 Macaca mulatta 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 18 and 19). 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, multi-
nucleated 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.
159
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Figure 18. Drawing of tissue from heart of monkey
fed 2,3,7,8-TCDD; tissue fixed with formalin and
stained with hematoxylin and eosin. Muscle cells
are hypertrophic with enlarged and distorted nuclei.
X115.
(Source: Redrawn from Norback and Allen 1973)
160
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••• • ' f•
•••&»-'
• .-^4:
• • ** /
'•*3,!&&.&:
MYOFIBRILS
MITOCHONDRION
Figure 19. 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)
161
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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 20. 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, sub-
cutaneous 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 gastro-
intestinal 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 archi-
tecture, as illustrated in Figures 21 through 24. 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 21). Individual hepato-
cytes 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 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 25). Congestion and elongation of the intestinal villi also were
noted.
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
162
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HAIR FOLLICLE
SMALL
KERATIN
CYST
LARGE
KERATIN CYST
Figure 20. 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 hair follicle. Tissue fixed with
formalin and stained with hematoxylin and eosin. X15.
(Source: Redrawn from Norback and Allen 1973)
163
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NUCLEI
Figure 21. Drawing of part of a multinucleated liver cell from a
female rat given 0.1 yg of 2,3,7,8-TCDD/kg/day for 2 years.
Uranyl acetate-lead citrate stain. X1620.
(Source: Redrawn from Kociba, et al.-1978)
164
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NUCLEUS
CELL
MEMBRANE
MITOCHONDRION
VESICLE
SMOOTH
ENDOPLASMIC
RETICULUM
ROUGH
ENDOPLASMIC
RETICULUM
CELL
MEMBRANE
LIPID DROPLET
LIPID DROPLETS
Figure 22. 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)
165
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NORMAL
MEMBRANES
Figure 23. Drawing of normal membrane junctions from
the periportal region of a test animal 42 days after administration of
200 yg/kg 2,3,7,8-TCDD.
Uranyl acetate and lead citrate stain. X16000.
(Source: Redrawn from Greig and Osborne 1978)
166
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t.is?'?«'" v ••"* "
Vg, fa • . » *(4
Figure 24. Drawing of distorted periportal membrane junction, showing
loss of continuity of plasma membranes between parenchyma! cells
(42 days after 200 yg/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)
167
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Figure 25. Focal alveolar hyperplasia near terminal bronchiole
within lung of rat given 2,3,7,8-TCDD at dosage of 0.1 yg/kg per day.
H&E Stain. X100.
(Source: Redrawn from Kociba et al. 1978)
168
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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.
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
31 and 32. 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).
Comparative Lethal Doses
Table 33 lists the LD50 values for various substituted dibenzo-para-
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 structure-activity relationships are
discussed in a later subsection. The LD50 values for 2,3,7,8-TCDD in rats,
guinea pigs, and rabbits are presented in Table 33. The male guinea pig
appears to be the most sensitive, having an LD50 of 0.0006 mg/kg (0.6
ug/kg). The LD50 values in monkeys exposed to a single oral dose range from
50 to 70 ug/kg body weight (McConnell, Moore, and Dalgard 1978). In mice,
the LD50 is 0.2837 mg/kg body weight (McConnell et al. 1978).
Target organs for the acute toxic effects of TCDD in commonly studied
laboratory animals are listed in Table 34. All species of animals studied
by Moore et al. (1976) showed severe thymus involution and testicular degen-
eration. 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 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 freshwater
aquatic life (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
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TABLE 31.
TOXICITIES OF ORGANIC PESTICIDES AND
2,3,7,8-TCDD3
Compound
2,3,7,8-TCDD
Disolfoton and Phorate
Diazinon
Parathion and Methyl parathion
Aldicarb
Malathion
Silvex (2,4,5-TP)
Hexachlorobenzene
Hexach]orophene
Toxaphene
MPCA
Pentachlorophenol
Butachlor
Methoxychlor
2,4,5-T
Bromacil
2,4-D
Ortho- and Paradichlorobenzene
Atrazine
Captan
Arachlor
Methyl methacralate
Di-n-butyl phthalate
Styrene
Maximum dose producing no
observed adverse effect,
mg/kg per day
_5
10
0.01
0.02
0.043
0.1
0.2
0.75
1
1
1.25
1.25
3
10
10
10
12.5
12.5
13.4
21.5
50
100
100
110
133
Source: National Academy of Science 1977.
170
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TABLE 32. ACUTE TOXICITIES OF.DIOXINS'
Substitutions with chlorine
None
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 .
1,2,3,4,6,7,8,9C
l-N02-3,7,8
l-NH2-3,7,8
l-N02-2,3,7,8
l-NH2-2,3,7,8
LD50 (ug/kg)b
Guinea pigs
>300,000
29,444
0.6-2
3.1
1,125
72.5
70-100
60-100 ,
>600;7180a
>30,000
>30,000
47.5
194.2
Mice
>50 x 103 (i.p.)e
>3,000
283.7
337.5
>5,000
825
1,250
> 1,440
>4 x 106
.>2,000
>4,800
P Unless otherwise noted, taken from McConnell et al. 1978.
All values are for oral doses unless noted; test period is 30 days.
World Health Organization, IARC Monographs on the Evaluation of the
H Carcinogenic Risk of Chemicals to Man. 15:69-70, August 1977.
a EPA-RPAR on Pentachlorophenol. Federal Register 43(202):48454, October
18, 1978.
e Interperitoneal.
TABLE 33. ACUTE TOXICITIES OF 2,3,7,8-TCDD
FOR VARIOUS SPECIES3
Species
Rat
Guinea pig
Rabbit
Sex
Male
Female
Male
Female
Female and male
Female and male
Female and male
Route of exposure
Oral
Oral
Oral
Oral
Oral
Dermal
Interperitoneal
Dosage,
LD50 mg/kg
0.022
0.045
0.0006
0.0021
0.115
0.272
>0.252
Source: Schwetz et al. 1973.
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TABLE 34. SUMMARY OF ACUTE TOXICITY EFFECTS OF 2,3,7,8-TCDDc
Mice
Guinea pigs
Monkeys
(female)
Thymus involution
Spleen reduction (white pulp)
Bone marrow hypoplasia
Liver, megalocytosis/
degeneration
Bile duct hyperplasia
Testicular degeneration
Renal pelvis hyperplasia
Urinary bladder hyperplasia
Adrenal cortical atrophy
(Zona Glomerulus)
Hemorrhage: Intestinal
Adrenal
Ascites
Cutaneous lesions
+++
N/A
Source: Moore et al. 1976. Key as follows:
- no effects
+ mildly affected
++ moderately affected
+++ severely affected
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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
jjg/liter under static conditions for 96 hours resulted in 12 percent
mortality, whereas mortality of control fish was 2 percent (Miller, Norn's,
and Hawks 1973). In the same study, all coho salmon exposed to 0.056
ug/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-para-dioxins
are presented earlier in this Section. Briefly, at least one hydrogen atom
and a minumum of three laterally placed halogen atoms must be present in the
dioxin structure for it to be toxic (Kende and Wade 1973).
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 on 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 nearly
every organ system. In addition to chloracne, another dermatologic mani-
festation 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 gonadatropin (pituitary
hormones influencing reproductive organs). A 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.
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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 are
active skin irritants and 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, derma-
titis 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-size 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 vesic-
ulobullous (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 2,3,7,8-TCDD. Their results indicate
that the dioxin depresses UD levels sufficiently to produce the biochemical
174
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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 insuffi-
ciency 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 ug/kg per day increased the levels of serum bilirubin and
alkaline phosphatase and caused pathologic changes in the liver; doses of
0.1 ug/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 ug/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 N-methyl-nicotinamide (NMN) in rats given 10, 25, or 50 ug/kg
2,3,7,8-TCDD. In the 10 ug/kg dose group, only NMN accumulation was
slightly decreased at 7 days. At 25 ug/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
ug/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.
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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 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 hydroxyla-
tion in the 2p- and 16a-positions has been reduced by 50 percent in rats
receiving less than I ug/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. 7a and 6p-hydroxylases active on 4-androstene-3,17-dione;
2. 7a and 2o hydroxylases active on 5a-androstane-3ot, 170-diol; and
3. 16or 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 35, 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).
176
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TABLE 35. EFFECTS OF IN VIVO 2,3,7,8-TCDD EXPOSURE ON FUNCTIONAL IMMUNOLOGICAL PARAMETERS1
Species
Parameter
Effect"
Reference
Guinea pig
Rat
Rat
Mouse
Rat, mouse
Rat
Mouse
Guinea pig
Rat
Delayed type hypersensitivity
Delayed type hypersensitivity
Graft versus host activity
Graft versus host activity
Rejection of skin allografts
Lymphocyte transformation by PHA
and Con A
Lymphocyte transformation by PHA
Antibody response to tetanus toxoid
Antibody response to bovine y-globulin
+d/-c
+c/-e
_c,f/+c,g
_d,f/_d,g
Vos et al. 1973
Moore and Faith 1976; Vos et al. 1973
Vos and Moore 1974
Vos and Moore 1974; Vos et al. 1973
Vos and Moore 1974
Vos and Moore 1974; Moore and Faith
1976
Vos and Moore 1974
Vos et al. 1973
Moore and Faith 1976
* Source: Vos et al. 1978.
Denotes the suppressive effect on immunological parameters +, slight; ++, moderate effect; -, no effect.
. Treatment of young animals.
Treatment during the perinatal period.
, Treatment of adult animals.
Primary antibody response.
* Secondary antibody response.
-------
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 prenatal ly 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 func-
tion 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).
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 bern and Herpesvirus suis. At dose schedules
of 1 |jg/kg weekly for 4 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-bluetetrazolium, 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
The process by which cells engulf and destroy foreign material.
178
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more susceptible to dioxin-Induced immune-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 platlets) and terminal elevated packed red cell volumes secondary
to hemoconcentration (Weissberg and 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 ug/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-para-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 ug/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 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 de-
creased 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
179
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irritability, aggressiveness, and restlessness in rats, without acquisition
or loss of a conditioned avoidance reflex. In this study, the dioxin stim-
ulated the activity of adenyl cyclase in the rat brain striatum and hypo-
thalmus 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 electro-
myography). 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 charac-
terize 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 mechanism 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 eval-
uate 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.
180
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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 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 ug/kg of
2,3,7,8-TCDD produced an increased rate of cleft palate; maximal teratogen-
icity 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 coworkers 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 coworkers (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-TCDD on days 10 to 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 ug/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 gesta-
tion 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 hemor-
rhages 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 infiltra-
tion of the liver, general edema, delayed head ossification, low birth-
weight, fetal resorptions, and embryo!ethality.
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 ug/kg level; but fetal
mortality, early and late resorptions, and fetal intestinal hemorrhage were
* Dilation of renal pelvis usually associated with an obstructed ureter.
181
-------
observed in groups given 0.125 to 2.0 ug/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). Neubert and Dillman (1972) determined that the
threshold dose of 2,4,5-T that produced an increase in embryolethality was
10 to 15 mg/kg, whereas 2,3,7,8-TCDD doses of 4.5 ug/kg produced marked
increases in embryolethality in NMRI mice. Cystic kidneys occurred
unilaterally in 58.9 percent and bilaterally in 36.3 percent of mice pups
exposed to 1 ug/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 ug/kg per day, but not at 0.001 ug/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 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-para-dioxin class of compounds (Courtney 1976). None of the
dibenzo-para-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-para-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, Lalich, and Allen 1977; Kociba et al. 1978; Toth et al. 1979). Van
Miller and coworkers exposed rats to diets containing the dioxin at concen-
trations 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 36, among the 23 animals with tumors, 5 had two primary neoplastic
(cancerous) lesions. Ingestion by rats of 0.1 ug/kg per day 2,3,7,8-TCDD
182
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TABLE 36. SUMMARY OF NEOPLASTIC ALTERATIONS OBSERVED IN RATS FED
SUBACUTE LEVELS OF 2,3,7,8-TCDD FOR 78 WEEKS3
Level
of 2,3,7,8-TCDD
0
1 pptc
5 ppt
50 ppt
500 ppt
1 ppb6
5 ppb
No. of animals,
with neoplasms
0
0
5
3
4
4
7
No. of neoplasms
0
0
6
3
4
5
10
Diagnosis
1 ear duct carcinoma
1 lymphocytic leukemia
1 adenocarcinoma (kidney)
1 malignant histiocytoma
(peritoneal)
1 angiosarcoma (skin)
1 Leydig cell adenoma
(testes)
1 fibrosarcoma (muscle)
1 squamous cell tumor
(skin)
1 astrocytoma (brain)
1 fibroma (striated
muscle)
1 carcinoma (skin)
1 adenocarcinoma (kidney)
1 sclerosing seminoma
(testes)
1 cholangiocarcinoma (liver)
1 angiosarcoma (skin)
1 glioblastoma (brain)
2 malignant histiocytomas
(peritoneal)
4 squamous cell tumors (lung)
4 neoplastic nodules (liver)
2 cholangiocarcinomas (liver)
a Source: VanMiller, Lalich, and Allen 1977.
10 animals per group.
^ 1 ppt = 10"12g 2,3,7,8-TCDD/g food.
Metastases observed.
e 1 ppb = 10"9g 2,3,7,8-TCDD/g food.
183
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for 2 years caused an increased incidence of hepatocellular carcinomas and
squamous cell carcinomas of the lung, hard palate/nasal turbi nates, or
tongue, and a reduced incidence of tumors of the pituitary, uterus, mammary
glands, pancreas, and adrenal glands (Kociba et al. 1978). Figures 26 and
27 illustrate the morphology of some of these lesions. In a recent study
with Swiss mice, Toth et al. (1979) showed that 2,4,5-trichlorophenoxy-
ethanol 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
Multiple studies have examined the effects of 2,3,7,8-TCDD administered
in combination with other known carcinogens in experimental animal test sys-
tems. Two studies used the two-stage tumori genesis assay of mouse skin
(Digiovanni et al. 1977; Berry et al. 1978). Berry and coworkers noted that
a dose of 0.1 ug 2,3,7,8-TCDD twice weekly was not sufficient to promote
skin tumors in mice treated with 7,12-demethylbenz(a) anthracene (DMBA).
Digiovanni found that at doses of 2 ug 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 non-
responsive 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-para-dioxins have been subjected to geno-
toxicity testing. These are unsubstituted dibenzo-para-dioxin, the 2,7-
dichloro-isomer, 2,3,7,8-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-para-
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 ab-
berations in bone marrow cells of rats (Khera and Ruddick 1973; Green,
Moreland, and Sheu 1977).
Mutagenicity
Table 37 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 investiga-
tions have obtained positive responses in Strain TA 1532, which detects
frameshift mutations.
Hussain et al . (1972) report the following results of mutagenicity
studies with 2,3,7,8-TCDD (99 percent) on three bacterial systems:
184
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FAT
DROPLETS
CANCER
CELLS
FIBROSIS
Figure 26. Lesion classified morphologically as hepatocellular
carcinoma in liver of rat given 0.1 yg 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)
185
-------
KERATINIZED
MATERIAL
Figure 27. Lesion within lung of rat given 0.1 yg 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. XI00.
(Source: Redrawn from Kociba et al. 1978)
186
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TABLE 37. MUTAGENICITY OF DIOXIN COMPOUNDS IN SALMONELLA TYPHIMURIUMC
Dioxin
isomer
Strains detecting base-pair substitutions
G46
2,3,7,8-TCDD 0
OCOD
Dibenzo-p-
dioxin
0
0
-
-
0
TA1530
0
0
-
-
-
0
TA1535
-
-
0
0
0
-
TA100
0
0
0
0
0
-
Strains detecting frameshifts
TA1531
0
0
0
7
-
0
TA1532
-
0
+
+
?
0
TA1534
0
0
0
7
•)
0
TA1537
-
0
0
0
0
-
TA1538
-
-
0
0
0
-
Reference
McCann 1975
Nebelt 1976
Hussain 1972
Seller 1973
Seller 1973
Commoner 1976
CO
. Source: Wassom, Huff, and Loprieno 1978.
0, not tested; -, negative results; +, positive results; ?, doubtful mutagen. Results obtained with different experimental
protocols.
-------
(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
|jg/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.
Seiler (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-para-
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
pg/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 ug 2,3,7,8-TCDD per
liter or to a 10~4 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 multi-nuclei 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 con-
ducted 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
188
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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 ug/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 and thus led to death or structural
disorganization. Similar results have been obtained by others (Buu-Hoi et
al. 1971; Kimbrough et 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-p-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
189
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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
ug/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.
EPIDEMIC-LOGICAL 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 ug of 2,3,7,8-TCDD on the skin can lead
to chloracne development. Chloracne may appear first 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 asso-
190
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dated 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 cutanea
tarda, 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 carbo-
hydrate 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 et al. (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 toxico-
logical 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 expo-
sure 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 approxi-
mately 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 suffered from delayed reactions, exper-
iencing abdominal pain, headache, excessive fatigue, uncharacteristic
episodes of anger, diminished concentration, other neurological distur-
bances, 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 hyperlipo-
proteinaemia. No other biochemical abnormalities were noted. Over a period
191
-------
of 6 months (after the onset of the delayed symptoms), the symptoms sub-
sided. All three scientists were aware of the danger involved in the sub-
stance 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 indus-
trial 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, exces-
sive perspiration, headache, and disorders of the mental and sexual func-
tions. One worker suffered and died from severe atherosclerosis, hyper-
tension, 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 photosensitivity 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 intox-
icated 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-
192
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TCDD and polychlorinated byphenyls as the causitive agents (Carter et al.
1975; Kimbrough et al. 1977). A 6-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 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 examina-
tion was performed, as well as urinalysis, a voiding cystogram, an intra-
venous 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 al. 1977). Three other individuals exposed to the arena developed
recurrent headaches, skin lesions, and polyarthralgia (Kimbrough et al.
1977).
In another sprayed arena, two 3-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 the
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 hyper-
tension, 9 cases of coronary insufficiency, 8 cases of muscular astenia
(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,
193
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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 popula-
tion. 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 popu-
lation. Eight percent of the screened population showed hepatomegally of
undetermined etiology, and some of the screened population showed elevated
levels of liver transaminases.
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 over a period of 5
years. Cancer registries, hospital discharge forms, notifications of infec-
tious 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).
194
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In the sprayed areas of Vietnam, doctors have cited increased inci-
dences 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 38 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 28 indicates
linear correlation. Highest rates of 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; 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 acci-
dent, 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).
195
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TABLE 38. COMBINED RATE OF NEURAL-TUBE DEFECTS IN NEW SOUTH WALES
AND PREVIOUS-YEAR USAGE OF 2,4,5-T IN AUSTRALIA
Year
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
Neural -tube defects
in N.S.W. , cases
per 1000 births
1.72
1.77
1.93
1.83
2.13
2.37
1.88
2.15
2.19
2.27
2.03
2.30
Usage of 2,4,5-T
in Australia in
previous year,
metric tons
90
105
188
213
201
282
170
256
241
287
466
482
Source: Field and Kerr 1979.
2,4,5-T acid in equivalent metric tons.
196
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o
o
o
i/i
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Careinogenicity
Ton That et al. (1973) report an increase in the proportion of prjmary
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 deter-
mined to be 5.3 for exposure to phenoxy acid and 6.6 for exposure to chlo-
rophenols. 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
phenoxy acetic 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.
Mutagem'city
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 chromatid and chromosomal breaks and rearrangements.
Cytogenetic studies indicate chromosomal damage to cells in maternal periph-
eral 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 spontan-
eously 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).
198
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Czeizel and Kiraly (1976) compared the frequency of chromosome aberra-
tions 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.
199
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VOLUME I
REFERENCES
Ackerman, D. G., et al. 1978. At-Sea Incineration of Herbicide Orange
Onboard the M/T Vulcanus. EPA-600/2-78-086.
Ahling, B., and A. Lindskog. 1977. Formation of Polychlorinated Dibenzo-
p-dioxins and Dibenzofurans During Combustion of a 2,4,5-T Formulation.
Chemosphere, 6(8):461-468.
Air/Water Pollution Report. 1978. Around the States—Kansas. June 5, p.
227.
Aitio, A., M. Parkki, and J. Marniemi. 1979. Different Effect of TCDD on
Glucuronide Conjugation of Various Aglycones: Studies in Wistar and Gunn
Rats. Toxicol. Appl. Pharmacol., 47:55-60.
Albro, P. W. 1978. Effects of TCDD on Lipid Profiles in Tissue of the
Fischer Rat. Chon-Biol. Interact., 23(3):315-30.
Allen, J., M.D. 1978. University of Wisconsin, personal communication,
August 28.
Allen, J. R. 1967. Light and Electron Microscopic Observations in Macaca
Mulatta Monkey Fed Toxic Fat. American Journal of Vet. Research, 28:1513-
26.
Allen, J. R., J. P. Van Miller, and D. H. Norback. 1975. Tissue Distri-
bution, Excretion and Biological Effects of [14C]-Tetrachlorodibenzo-p-
dioxin in Rats. Fd Cosmet. Toxicol., 13:501-505.
Allen, J. R., et al. 1975. Morphological Changes in Monkeys Consuming a
Diet Containing Low Levels of 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Fd
Cosmet. Toxicol., 15:401-410.
Allen, J. R. , et al. 1979. Toxicological Responses of Nonhuman Primates to
TCDD. Toxicol. Appl. Pharmacol., 48(1):A180.
American Broadcasting Co. 1978. Transcripts of broadcasts aired on July 25
and August 1. 20/20. New York.
American Industrial Hygiene Association Journal. 1980. No Excess in Cancer
Deaths Found in Largest Group Ever Studied for Long-Term Effects of Dioxin
Exposure. January.
200
-------
American Wood Preservers Institute. 1977. Memorandum to the Office of
Pesticide Programs, U.S. Environmental Protection Agency. Pentachloro-
phenol: A Wood Preservative. Research Triangle Park, North Carolina.
Anaizi, N. H. , and J. Cohen. 1979. The Effects of TCDD on the Renal
Tubular Secretion of Phenolsulfonphthalein. J. Pharmacol. Exp. Ther.,
207(3):748-755.
Anderson, J. 1978. The Poisoning of America. The Washington Post, United
Feature Syndicate, Inc., July 15.
Aniline, 0. 1973. Preparation of Chlorodibenzo-p-dioxins for Toxicological
Evaluation. In: Chlorodioxins—Origin and Fate, E. H. Blair, ed. American
Chemical Society, Washington, D.C., pp. 126-135.
Arsenault, R. D. 1976. Pentachlorophenol and Contained Chlorinated
Dibenzodioxins in the Environment. American Wood Preservers Association.
Auer, C. 1979. EPA Office of Toxic Substances, personal communication with
D. R. Watkins, EPA, lERL-Cincinnati, February 26.
American Wood Preservers Institute Directory. 1977. AE Concepts in Wood
Design, No. 17, September-October.
Bage, G. , E. Cekanova, and K. S. Larsson. 1973. Teratogenic and Embryo-
toxic Effects of the Herbicides Di- and Trichlorophenoxyacetic Acids (2,4-D
and 2,4,5-T). Acta Pharmacol. et Toxicol., 32:408-416.
Bail in, L. J. 1977. Microwave Plasma Detoxification Process for Hazardous
Wastes. EPA, MERL-Cincinnati, EPA Contract No. 68-03-2190, October.
Bail in, L. J. 1978a. Smithsonian Science Information Exchange Notice of
Research Project Microwave Regeneration of Activated Carbon. EPA Contract
No. 68-03-2660, March 1.
Bail in, L. J. 1978b. Summary Report: Detoxification of Navy Red Dye by
Microwave Plasma. EPA-600/2-78-081, June.
Bailin, L. J., and B. L. Hertzler. 1976. Development of Microwave Plasma
Detoxification Process for Hazardous Wastes: Phase I, EPA Contract No.
68-03-2190.
Bailin, L. J. , and E. L. Littauer. 1978. Microwave Regeneration of Acti-
vated Carbon. EPA, lERL-Cincinnati, Contract No. 68-03-2660, March.
Ball, L. M. , and R. S. Chhabra. 1977. Effects of Environmental Pollutants
on the Intestinal Absorption of Nutrients. Environmental Health Perspec-
tives, 20:231.
Barbero, R. D. 1978. Response Report: Dioxins in Sludges From the Manu-
facture of: Trichlorophenol, Pentachlorophenol, and Hexachlorophene. CBC
Associates, Inc., Falls Church, Virginia. Unpublished.
201
-------
Barsotti, D. A., L. J. Abrahamson, and J. R. Allen. 1979. Hormonal Alter-
ations in Female Rhesus Monkeys Fed A Diet Containing TCDD. Bulletin of
Environmental Contamination and Toxicology, 21:463-469.
Bartleson, F. D. , Jr. , D. D. Harrison, and J. B. Morgan. 1975. Field
Studies of Wildlife Exposed to TCDD Contaminated Soils. Air Force Armament
Lab. Eglin A.F. Base, Florida.
Baughman, R. , and M. Meselson. 1973. An Analytical Method for Detecting
TCDD (Dioxin): Levels of TCDD in Samples From Vietnam. Environmental
Health Perspectives, 5:27-35, September.
Baughman, R. W. 1974. Ph.D. Thesis, Harvard University, Boston.
Beale, M. G. , et al. 1977. Long-Term Effects of Dioxin Exposure. Lancet,
1(8014):788, April.
Beatty, P. 1977. Studies of Metabolism and Possible Mechanisms of Toxicity
of TCDD, Thesis, Vanderbilt University, Nashville, Tennessee.
Beatty, P. W. , and R. A. Neal. 1976. Induction of DT-diaphorase Activity
of Rat Liver by 2,3,7,8-TCDD (Abstract No. 232). Toxicol. Appl. Pharmacol.,
37:189.
Beatty, P. W. , et al. 1978. Effect of Alteration of Rat Hepatic Mixed
Function Oxidose (MFO) Activity On the Toxicity of 2,3,7,8-TCDD. Toxicol.
Appl. Pharmacol., 45(2):513-20.
Becker, D. 1973. The Effect of Folate Overdose and of 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin (TCDBD) on Kidney and Liver Respectively of Rat and Mouse
Embryos. Teratology, 8:215.
Benedetto, A. V. , and J. S. Taylor. 1978. Porphyria Cutanea Tarda: Update
1978. Cutis, 21:983-88, April.
Berry, D. L. , et al. 1978. Lack of Tumor-Promoting Ability of Certain
Environmental Chemicals in A Two-Stage Mouse Skin Tumorigenesis Assay. Res.
Comm. Chem. Path, and Pharm., 20(1): 101-108, April.
Bertoni, G. , et al. 1978. Gas Chromatographic Determination of 2,3,7,8-
TCDD in the Experimental Decontamination of Seveso Soil by Ultraviolet
Radiation. Analytical Chemistry, 50(6):732-735.
Bevenue, A., and H. Beckman. 1967. Pentachlorophenol: A Discussion of its
Properties and its Occurrence as a Residue in Human and Animal Tissues.
Residue Reviews, 19:83-129.
Blair, G. H. 1979. The Safety of 2,4,5-T. Science, 206:1135-6, December.
Blair, E. H. , K. C. Kaner, and E. E. Kenaga. 1963. Synthesis and Insec-
ticidal Activity of 0-methyl 0-(2,4,5-Trichlorophenyl) Phosphoramidothioates
and Related Compounds. J. Agric. Food Chem., 11(3):237-240.
202
-------
Blum, B. 1979. U.S. EPA Deputy Administrator, Press Conference Statement:
Emergency Action to Stop Spraying of the Herbicides 2,4,5-T and Silvex.
Also U.S. EPA Environmental News release, March 1.
Boer, F. P., et al. 1971. X-ray Diffraction Studies of Chlorinated
Dibenzo-p-dioxins. In: Chlorodioxins—Origin and Fate, E. Blair, ed.
American Chem. Society, Washington, D.C., pp. 14-15.
Bolton, L. 1978. Seveso Dioxin: No Solution in Sight. Chem. Eng.,
85(22):78, October 9.
Bonaccorsi, A., R. Panelli, and G. Tognoni. 1978. In the Wake of Seveso.
Ambio, 7(5-6):234-239.
Boobis, A. R. 1979. Effects of Microsomal System Inducers in Vivo and
Inhibitors in Vitro on the Covalent Binding of Benzo(a) pyrene Metabolites
to DNA Catalyzed by Liver Microsomes from Genetically Responsive and Non-
responsive Mice. Biochemical Pharmacology, 28(1):111-122.
Botre, C., A. Memoli, and F. Alhaique. 1978. TCDD Solubilization and
Photodecomposition in Aqueous Solutions. Environmental Science and Tech-
nology, 12(3):335-336.
Botre, C., A. Memoli, and F. Alhaique. 1979. On the Degradation of
2,3,7,8-tetrachlorodibenzo-para dioxin (TCDD) by Means of a New Class of
Chloriodides. Environmental Science and Technology, 13(2):228-231.
Bowes, G. W., et al. 1973. The Search for Chlorinated Dibenzofurans and
Chlorinated Dibenzodioxins in Wildlife Populations Showing Elevated Levels
of Embryonic Death. Environmental Health Perspectives, 5:191-8, September.
Bradlaw, J. A. 1979. Induction of Enzyme Activity in Cell Culture: A
Rapid Screen for Detection of Planar Polychlorinated Organic Compounds. J.
Assoc. Offic. Anal. Chem., 62:904-916.
Brugger, J. E. 1978. Use of Mobile Incinerator to Dispose of p-Dioxin.
Written communication to K. Q. Camin, Regional Administrator, EPA Region
VII, from U.S. EPA, OHMSB, lERL-Ci, June 16.
Buser, H. R. 1975. Polychlorinated Dibenzo-p-dioxin: Separation and
Identification of Isomers by Gas Chromatography—Mass Spectrometry. J.
Chromatography, 114:95-108.
Buser, H. R. 1976. Preparation of Qualitative Standard Mixtures of Poly-
chlorinated Dibenzo-p-Dioxins and Dibenzofurans by Ultraviolet and
y-Irradiation of the Octachloro Compounds. J. Chromatography, 129:303-7.
Buser, H. R. 1978. Polychlorinated Dibenzo-p-dioxins and Dibenzofurans:
Formation, Occurrence and Analysis of Environmentally Hazardous Compounds.
Department of Organic Chemistry, University of Umea, Sweden, and Swiss
Federal Research Station, Waedenswil, Switzerland, pp. 9-21.
203
-------
Buser, H. R. 1979a. Formation and Identification of Tetra-and Pentachlo-
rodibenzo-p-dioxins from Photolysis of Two Isomeric Hexachlorodibenzo-p-
dioxins. Chemosphere, 4:251-257.
Buser, H. R. 1979b. Formation of Polychlorinated Dibenzofurans (PCDF's)
and Dibenzo-p-dioxins (PCDD's) from the Pyrolysis of Chlorobenzenes.
Chemosphere, 6:415-424.
Buser, H. R., and H. P. Bosshardt. 1974. Determination of 2,3,7,8-Tetra-
chlorodibenzo 1,4 dioxin at Parts Per Billion Levels in Technical Grade
2,4,5-Trichlorophenoxyacetic Acid, in 2,4,5-T Alkyl Ester and 2,4,5-T Amine
Salt Herbicide Formulations by Quadrupole Mass Fragmentography. J. Chrom-
atography, 90:71-77.
Buser, H. R., and H. P. Bosshardt. 1976. Determination of Polychlorinated
Dibenzo-p-dioxins and Dibenzofurans in Commercial Pentachlorophenols by
Combined GC-MS. Journal of the AOAC, 59(3):562-569.
Buser, H. R., and H. P. Bosshardt. 1978. Polychlorinated Dibenzo-p-
dioxins, Dibenzofurans and Benzenes in the Fly Ash of Municipal and Indus-
trial Incinerators. Mitt. Geb. Lebensmittelsunters Hyg., 69(2):191-199.
Buser, H. R., and C. Rappe. 1978. Identification of Substitution Patterns
In Polychlorinated Dibenzo-p-Dioxins (PCDD's) by Mass Spectrometry. Chem-
osphere, 7(2):199-211.
Buser, H. R., H. P. Bosshardt, and C. Rappe. 1978. Identification of
Polychlorinated Dibenzo-p-Dioxin-Isomers Formed in Fly Ash. Chemosphere,
7(2): 165-172.
Buu-Hoi, N. P., et al. 1971. Properties Canceramimetiques de la Tetra-
chloro 2,3,7,8 Dibenzo-p-dioxins. C.R. Acad. Sci. (Paris), 272:1447-1450.
Buu-Hoi, N. P., et al. 1972. Organs as Targets of "Dioxin" (2,3,7,8-TCDD)
Intoxication. Naturwissenschaften, 59:174.
Campbell, K. 1979. Effect of Exposure to Chemical Contaminants on Suscep-
tibility to Infection By Pathogenic Organisms. Tox. Research Proj. Direc-
tory, 04:05.
Carlstedt-Duke, J. M. 1979. B. Tissue Distribution of the Receptor for
TCDD in the Rat. Cancer Research, Issue 8, 39:3172-3176.
Carreri, V. 1978. Review of the Events Which Occurred in Seveso. In:
Dioxin Toxicological and Chemical Aspects, F. Cattabeni, A. Cavallaro, and
G. Galli, eds. SP Medical and Scientific Books. Spectrum Publications,
Inc., New York, London, pp. 1-4.
Carter, C. D., et al. 1975. Tetrachlorodibenzodioxin: An Accidental
Poisoning Episode in Horse Arenas. Science, 188(4189): 738-740.
204
-------
Cassito, L., and P. Magni. 1977. Method for Emission Control at the Pro-
posed Seveso Incinerating Plant Using Gas Chromatography and Mass Frag-
mentography. Inquinamento, 19(5):33-38.
Cattabeni, F., et al. 1978. DIOXIN: Toxicological and Chemical Aspects.
SP Medical and Scientific Books, New York.
Cavolloni, L., and L. Zecca. 1977. La Decomposizione Del TCDD Mediante
Ozono. Medicina Termale e Climatologia, 34:73-74.
CEFIC. 1978. Biodegradation Status Report. Safety of Chemicals Committee,
Biodegradation Task Force, Brussels, February, p. 9.
Chem. and Eng. News. 1974a. Vietnam Foliage Hit Hard by Herbicides.
52(9):6-7, March 4.
Chem. and Eng. News. 1974b. War Herbicide Report Stirs Controversy.
52(10):18-19, March 11.
Chem and Eng. News. 1978. Old Landfill Site Poses Health Problems. August
7, p. 6.
Chemical Engineering. 1978. British Plant Shut Because of Health Risk.
September 11, p. 107.
Chemical Regulation Reporter. 1978. Pentachlorophenol: Study Group
Advises Using Controls to Reduce Dioxin Impurity Levels. Vol. 2, No. 1,
April 7, pp. 6-7.
Chemical Regulation Reporter. 1979a. Reports on Bioassays of Three
Chemicals Available From National Cancer Institute. March 2, p. 216.
Chemical Regulation Reporter. 1979b. Hooker Chemicals Installing Toxic
Controls at Montague, Michigan, Site. June 22, pp. 457-458.
Chemical Regulation Reporter. 1979c. Ban On All Remaining Uses of 2,4,5-T,
Si 1 vex to be Considered at Hearings. July 13, p. 529-30.
Chemical Regulation Reporter. 1980a. NIOSH Finds Dioxin, Carcinogens in
Plant Dust Samples Near Landfill. January 11, p. 1593.
Chemical Regulation Reporter 1980b. Dioxins: EPA Finds No Detectable
Levels of TCDD in Mother's Milk Samples. January 18, p. 1620.
Chemical Week. 1977. Detoxifying Dioxin. November 23, p. 17.
Chemical Week. 1978a. Dioxin Lingers On. April 12.
Chemical Week. 1978b. Dioxin Down Under. May 10.
205
-------
Chemical Week. 1978c. Checking Dioxin. May 17.
Chemical Week. 1978d. 2,4,5-T Under Fire. June 14.
Chemical Week. 1978e. Scrubdown for Dioxin. June 21.
Chemical Week. 1979a. Hooker Dumpsites May Pose Dioxin Threat. 124(1):16,
January 3.
Chemical Week. 1979b. Faulty Reporting of Seveso Birth Defects. 124(9),
February 28.
Chemical Week. 1979c. More Agent Orange Suits Filed in Chicago; Still
Others Will Follow. 124(9), February 28.
Chemical Week. 1979d. Still More Hassles For Hooker. April 25, p. 23.
Chemical Week. 1979e. Dioxin is Found in Cleanup Worker's Blood. May 23.
Chemical Week. 1979f. Discovery of Dioxin At Montague Could Impede Accord
on Hooker Wastes. June 6, p. 18.
Chemical Week. 1979g. Global Marine Will Burn Chemical Wastes at Sea.
July 11.
Chemical Week. 1979h. Seveso Cleanup Still Not Solved. July 18.
Chemical Week. 1979i. Suits Boost Claims for Dioxin-Spill Damage. July
25.
Chem. Sources-U.S.A. 1975. Directories Publishing Co., Inc., Flemington,
New Jersey.
Chulkov, Y. I., V. Parini, and B. Staroselets. 1937. The Action of Chlo-
rine on Phenol in Alkaline Solution and a Possible Method for Preparation of
Chloranil. Chemical Abstracts, 31:4967.
Ciaccio, E. I. 1979. Dioxin Contamination. Chemical and Engineering News,
April 16, p. 3.
Cincinnati Enquirer. 1978a. Chemical Dumps Proving Hazardous. August 6.
Cincinnati Enquirer. 1978b. Residents Near Canal Fear Poisoning. August
6.
Cincinnati Enquirer. 1978c. Grass-Roots Protest Forming Over Spraying of
Herbicide. August 20, p. J-6.
Cincinnati Enquirer. 1979. Bayou Closed by Herbicide. August 23.
206
-------
Cleary, T. F. 1971. Production of 2,3-Methylenebis (3,4,6-Trichloro-
phenol). Centerchem., Inc., September 21.
Cocucci, S. , et al. 1979. Absorption and Translocation of Tetrachloro-
dibenzo-p-dioxine by Plants From Polluted Soil. Experientia, 35(4):482-484.
Colledge, C. 1978. U.S. EPA Technical Services Div., personal communica-
tion, August 21.
Collins, T. F. X., and C. H. Williams. 1971. Teratogenic Studies With
2,4,5-T and 2,4-D in the Hamster. Bulletin of Environmental Contamination
and Toxicology, 6(6):559-567.
Commoner, B. 1976. Reliability of Bacteria Mutagenesis Techniques to
Distinguish Carcinogenic and Noncarcinogenic Chemicals, EPA-600/1-76-022, 1-
103.
Commoner, B. 1977. Seveso: The Tragedy Lingers On. Hospital Practice,
pp. 31, 33.
Commoner, B., and R. E. Scott. 1976a. Accidental Contamination of Soil
with Dioxin in Missouri: Effects and Countermeasures. Center for the
Biology of Natural Systems. Washington University, St. Louis, Missouri.
Commoner, B., and R. E. Scott. 1976b. U.S.A.F. Studies on the Stability
and Ecological Effects of TCDD (Dioxin): An Evaluation Relative to the
Accidental Dissemination of TCDD at Seveso, Italy. Center for the Biology
of Natural Systems, Washington University, St. Louis, Missouri.
Cookson, C. 1979. 'Emergency' Ban on 2,4,5-T Herbicide in U.S. Nature
278:108-109, March 8.
Cooper, J. J., and W. H. Dennis, Jr. 1978. Catalytic Dechlorination of
Organochlorine Compounds IV: Mass Spectral Identification of DDT and Hepta-
chlor Products. Chemosphere, 4:229-305.
Cosmestic, Toiletry and Fragrance Association, Inc. 1977. CTFA Cosmetic
Ingredient Dictionary, 2nd Ed., Washington, D.C.
Courtney, K. D. 1970. Teratogenic Evaluation of 2,4,5-T. Science,
168:864-866, May.
Courtney, K. D. 1976. Mouse Teratology Studies With Chlorodibenzo-p-
dioxins. Bulletin of Environmental Contamination and Toxicology,
16(6):674-681.
Courtney, K. D., and J. A. Moore. 1971. Teratology Studies with 2,4,5-
Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
Toxicol. Appl. Pharmacol., 20:396-403.
207
-------
Courtney, K. D., M. T. Ebron, and A. W. Tucker. 1977. Distribution of
2,4,5-Trichlorophenoxyacetic Acid in the Mouse Fetus. Tox. Letters,
1:103-108.
Courtney, K. D., et al. 1978. Metabolic Studies with TCDD (Dioxin) Treated
Rats. Alch. Environ. Contam. Toxicol., 7:385-396.
Cox, J. M., B. A. Wright, and W. W. Wright. 1965. Thermal Degradation of
Poly (phenylene Oxides). J. Appl. Polymer Sci., 9:513-522.
Craft, T. F., R. D. Kimbrough, and C. T. Brown. 1975. Radiation Treatment
of High Strength Chlorinated Hydrocarbon Wastes, U.S. EPA-660/2-75-017.
Creso, E., et al. 1978. Neuropsychopharmacological Effect of TCDD.
Boll-Soc. Ital. Biol. Sper., 54:1512-1516.
Crosby, D. G. 1969. Experimental Approaches to Pesticide Photodecomposi-
tion. Residue Reviews, 25:1-12.
Crosby, D. G. 1978a. Conquering the Monster—The Photochemical Destruction
of Chlorodioxins. In: Proceedings of American Chem. Soc. Symposium on
Disposal and Decontamination of Pesticides, pp. 1-12.
Crosby, D. G. 1978b. University of California, Davis, personal communica-
tion, August 21.
Crosby, D. G., and A. S. Wong. 1973. Photochemical Generation of Chlo-
rinated Dioxins. Chemosphere, 5(5):327-332.
Crosby, D. G., and A. S. Wong. 1977. Environmental Degradation of
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Science, 195: 1337-1338, March
25.
Crosby, D. G., K. W. Moilanen, and A. S. Wong. 1973. Environmental Gener-
ation and Degradation of Dibenzodioxins and Dibenzofurans. Environmental
Health Perspectives, 5:259-265, September.
Crosby, D. G., et al. 1971. Photodecomposition of Chlorinated Dibenzo-p-
Dioxins. Science, 73:748-749, August 20.
Crossland, J., and K. Shea. 1973. The Hazard of Impurities. Environment,
15(5):35-38, June.
Crow, K. D. 1977. Effects of Dioxin Exposure. Lancet, 8028: 82-83, July
9.
Crow, K. D. 1978. Chloracne - An Up to Date Assessment. Ann. Occup. Hyg.,
21(3):297-8.
Crummett, W. B., and R. H. Stehl. 1973. Determination of Chlorinated
Dibenzo-p-dioxins and Dibenzofurans in Various Materials. Environmental
Health Perspectives. 5:15-25, September.
208
-------
Czeizel, E. , and J. Kiraly. 1976. Chromosome Exam in Workers Producing
Klounal and Buvinol in the Development of a Pesticide as a Complex Scientif-
ic Task, L. Banki, ed. Medicina, Budapest, pp. 239-256.
Davring, L. , and M. Summer. 1971. Cytogenetic Effects of 2,4,5-Trichloro-
phenoxyacetic Acid on Oogenesis and Early Embryo-genesis in Drosophila
Melanogaster. Hereditas, 68:115-122.
Deinaer, M. , et al. 1979. Isolation and Identification of Suspected Toxi-
cants in Pentachlorophenol. Presented Before the Division of Environmental
Chemistry, American Chemical Society, Honolulu, Hawaii, April.
Dennis, W. H. , Jr. 1972. Methods of Chemical Degradation of Pesticides and
Herbicides—A Review. NTIS AD-752 123.
Dennis, W. H. , Jr., and W. J. Cooper. 1975. Catalytic Dechlorination of
Organochlorine Compounds. I. DDT. Bulletin of Environmental Contamination
and Toxicology, 14(6):738-744.
Dennis, W. H. , Jr. , and W. J. Cooper. 1976. II. Heptachlor and Chlordane.
Bulletin of Environmental Contamination and Toxicology, 16(4):425-430.
Dennis, W. H. , Jr., and W. J. Cooper. 1977. III. Lindane. Bulletin of
Environmental Contamination and Toxicology. 18(l):57-59.
Diamond Alkalai Company. 1952. Improvements in or Relating to the Prepara-
tion of Chlor-substituted Ethylene Derivatives. The Patent Office. Patent
No. 673,565, London, June 23.
Dickson, J. P. 1978. Written communication to D. Watkins, U.S. EPA, IERL-
Cincinnati, from State Pollution Control Commission, Sydney, Australia.
DiGiovanni, J. , et al. 1977. (TCDD) and Arochlor 1254 in the Two-Stage
System of Mouse Skin Carcinogenesis. Bulletin of Environmental Contamina-
tion and Toxicology, 18(5):552-57.
DiGiovanni, J. , et al. 1979. 2,3,7,8-TCDD: Potent Anticarcinogenic Activ-
ity in CD-I Mice. Biochem. and Biophys. Res. Comm., 86(3):577-84, February.
Doedens, J. D. 1964. Chlorophenols. Kirk-Othmer, Second edition. Vol. 5,
pp. 325-338.
Dombrowski, D. , ed. 1978. Toxic Materials News, 5(33):236, August 16,
Silver Springs, Maryland.
Dorman, L. F. 1978. President of American Wood Preservers Inst., personal
communication, August 22, and September 5.
Dow Chemical Company. 1978. The Trace Chemistries of Fire—A Source of and
Routes for the Entry of Chlorinated Dioxins Into the Environment. The
Chlorinated Dioxin Task Force, the Michigan Division, Dow Chemical, U.S.A.
209
-------
Duqois, P., et al. 1967. Acne, Chlorique Collective et Accidentelle d'un
Type Nouveau. Bull Soc. Franc. Derm. Syph., 75, 260-261.
Duvall, D. S. , and W. A. Rubey. 1976. Laboratory Evaluation of High^Teitr
perature Destruction of Kepone and Related Pesticides. Tech. Rep.
UDRI-TR-76-21. University of Dayton Research Institute. EPA-600/2-76-299.
Duvall, D. S. , W. A. Rubey, and J. A. Mescher. 1978. Laboratory Charac-
terization of the Thermal Decomposition of Hazardous Wastes. In: Pro-
ceedings of the Fourth Annual Research Symposium--Land Disposal of Hazardous
Wastes. EPA 600/9-78-016.
Eaton, D. L. , 1979b. Characteristics of Hepatic Transport Systems in
Isolated Rat Hepatic Parenchynal Cells. Diss. Abstract. Int. B. ,
39(11):5337.
Eaton, D. L. 1979a. Alterations in Hepatic Transport Systems in Isolated
Rat Hepatocytes after Treatment with Microsomal Enzyme Induced. Toxicol.
Appl. Pharmacol., 48(1):A187.
Elovaara, E. , et al. 1977. Neurochemical Effects of 2,3,7,8-TCDD in Wistor
and Gunn Rats. Res. Commun. Chem. Pathol. Pharmacol., 18(3):487-94.
Elvidge, D. H. 1971. The Gas-Chromatographic Determination of
2,3,7,8-Tetrachlorodibenzo-p-dioxin in 2,4,5-Trichlorophenoxyacetic Acid
("2,4,5-T"), 2,4,5-T Esters and 2,4,5-Trichlorophenol. Analyst, 96:721-727.
Ensign, T. , and M. Uhi. 1978. Dioxin: Uncovered by Accident, The Number
of Cases is Rising Dramatically. In These Times, July 19-25, p. 16.
Environment Reporter. 1978. EPA to Investigate Possible Link Between
Herbicide Use, Miscarriages. 9(16):670-671, August 18.
Environment Reporter. 1979a. EPA Cites Miscarriage Correlation in Imposing
Emergency Ban on 2,4,5-T. March 9, p. 2074-S.
Environment Reporter. 1979b. Arkansas - Administrative Order Requires
Cleanup of Dioxin Wastes At Vertac, Inc., Site. June 22.
Epstein, S. S. 1970. A Family Likeness. Environment, 12(6):16-25.
Erk, S. D. , M. L. Taylor, and T. 0. Tiernan. 1979. Determination of
2,3,7,8-Tetrachlorodibenzo-p-dioxin Residues on Metal Surfaces by GC-MS.
Chemosphere 1:7-14.
Ernst and Ernst. 1977. Wood Preservation Statistics 1976. In: AWPA
Proceedings, pp. 181-217.
Fadiman, A. 1979. A Poisoned Town. Life Magazine, September, pp. 43-46,
49.
Faith, R. E. , and M. I. Luster. 1977. Modulation of Immune Function by
Chemicals of Environmental Concern. Environmental Health Perspectives,
20:245.
210
-------
Fanelli, R. , et al. 1978. Degradation of 2,3,7,8-Tetrachlorodibenzo-p-
dioxin in Organic Solvents by Gamma Ray Irradiation. Experientia,
34(9):1126-27, September 9.
Fanelli, R. , et al. 1979. Studies of TCDD Levels in Animals Living in the
Seveso Area. Presented in Rome at the Meeting of the Expert Committee of
the National Academy of Sciences, March 5-6.
Fanelli, R. , et al. 1980a. Presence of 2,3,7,8-Tetrachlorodibenzo-p-dioxin
in Wildlife Living Near Seveso, Italy: A Preliminary Study. Institute de
Ricerche Farmacologiche "Mario Negri," Milan, Italy. Prepublication copy.
Fanelli, R. , et al. 1980b. 2,3,7,8-TCDD Levels in Cow's Milk From the
Contaminated Area of Seveso. Mario Negri Institute for Pharmacological
Research, Milan, Italy. Prepublication copy.
Fara, G. M. 1977. Seveso--Studies in Teratogenic and Other Chronic Effects
of Chemical Pollutants Following an Accident in a Chemical Plant. Tera-
tology, 16:365.
Farbenind, I. G. 1934. Diary! Sulfides. Chemical Abstracts, 28:179.
Federal Working Group on Pest Management. 1974. Occupational Exposure to
Pesticides. Washington, D.C.
Ferguson, T. L., et al. 1975. Determination of Incinerator Operating
Conditions Necessary for Safe Disposal of Pesticides. EPA-600/2-75-041.
Field, B., and C. Kerr. 1979. Herbicide Use and Incidence of Neural Tube
Defects. Lancet, 1(8130):1341-1342.
Firestone, D. 1973. Etiology of Chick Edema Disease. Environmental Health
Perspectives, 5:59-66.
Firestone, D. 1977. The Determination of Polychlorodibenzo-p-dioxin and
Polychlorodibenzofurans in Commercial Gelatins by Gas-Li quid Chromatography.
J. Agric. Food Chem., 25(6):1275-1280.
Firestone, D. 1978. The 2,3,7,8-Tetrachlorodibenzo-para-dioxin Problem: A
Review. In: Chlorinated Phenoxy Acids and their Dioxins: Mode of Action,
Health Risks, and Environmental Effects, C. Ramel, ed. Ecol. Bull.
(Stockholm).
Firestone, D., et al. 1972. Determination of Polychloro-dibenzo-p-dioxins
and Related Compounds in Commercial Chlorophenols. Journal of the AOAC,
55(l):85-92.
Fishbein, L. 1978. Overview of Potential Mutagenic Problems Posed by Some
Pesticides and their Trace Impurities. Environmental Health Perspectives,
27:125-131.
211
-------
Fowler, B. A. , G. E. R. Hood, and G. W. Lucier. 1975. Tetrachlorodibenzo-
p-dioxin Induction of Renal Microsomal Enzyme Systems. Toxicol. Appl.
Pharmacol., 33:176-177.
Fox, J. L. 1979. Research Solving Body's Detoxifying System. Chem. and
Eng. News, 24-25, June 6.
Frigerio, A. 1978. The Seveso Case: TCDD in Animals from Contaminated
Areas. Methodol. Surv. Biochem., 7:161-6.
Fuller, J. G. 1977. The Poison That Fell From the Sky. Readers Digest,
August, pp. 192-236.
Galet, A. 1952. The Preparation of 2,4,5-Trichlorophenoxyacetic Acid
(2,4,5-T). J. Am. Chem. Soc., 74:3890.
Galston, A. W. 1975. The Ungreening of South Vietnam. Natural History,
83(6):10,12,14.
Galston, A. W. 1979. Herbicides: A Mixed Blessing. Bioscience,
29(2):85-89, February.
Gasiewicz, T. A., and R. A. Neal. 1978. Tissue Distribution and Excretion
of 2,3,7,8-TCDD and Effects Upon Clinical Chemical Parameters In the Guinea
Pig. Fed. Proc. Fed. Am. Soc. Exp. Biol., 37(3):501.
Gebfuigi, I., R. Baumann, and F. Korte. 1977. Photochemical Degradation of
2,3,7,8-TCDD Under Simulated Environmental Conditions. Naturwissenschaften,
64(9):486-7.
General Accounting Office. 1979. Health Effects of Exposure to Herbicide
Orange in South Vietnam Should be Resolved. Report by the Comptroller
General, CED-79-22, April 6.
Getzendaner, M. D., N. H. Mahle, and H. S. Higgins. 1977. Search for the
Presence of 2,3,7,8-Jetrachlorodibenzo-p-dioxin in Bovine Milk. Bulletin of
Environmental Contamination and Toxicology, 18:2.
Gilman and Dietrich. 1957. Halogen Derivatives of Dibenzo-p-dioxin.
79:1439.
Goldmann, P. J. 1972. Extremely Severe Acute Chloracne Due to Trichloro-
phenol Decomposition Products. Industrial Medicine, Social Medicine,
Industrial Hygiene, 7(1):12-18, January.
Goldmann, P. J. 1973. Schwerste Acute Chloracne, Eine Massenintoxikation
Durch 2,3,6,7-Tetrachlordibenzo-dioxin. From Int. Agency for Research on
Cancer. Der Hautarzt, 24:149-152.
Goldstein, J. A. 1979. The Structure-Activity Relationships of Halogenated
Biphenyls as Enzyme Inducers. Ann. New York Acad. Sci., 320:164-178.
212
-------
Goldstein, J. A., et al. 1978. Effects of Pentachlprophenol on Hepatic
Drug Metabolism and Pprphyria Related to Contamination with Chlorinated
Dibenzo-p-Dioxins. Environmental Protection Agency, Research Triangle Park,
North Carolina.
Goldston, A. W. 1978. Herbicides: A Mixed Blessing. Bio-Science,
29(2):85-89, February.
Goodell, (Senator). 1970. Authorization of Appropriations for Military
Procurement During Fiscal Year 1971-Amendment. Congressional Record-Senate,
July 16, pp. 24661-24670.
Grant, W. F. 1979. The Genotoxic Effects of 2,4,5-T. Mutation Res.,
65(2):83-119.
Gray, A. P., et al. 1976. Synthesis of Specific Polychlorinated Dibenzo-
p-dioxins. J. Org. Chem., 41(14):2435-2437.
Green, S., and F. S. Moreland. 1975. Cytogenetic Evaluation of Several
Dioxins in the Rat (Abstract No. 99). Toxicol. Appl. Pharmacol., 33:161.
Green, S., F. S. Moreland, and C. Sheu. 1977. Cytogenetic Effects of
2,3,7,8-TCDD on Rat Bone Marrow Cells. FDA By Lines, 6:292-294.
Greig, J. B., and G. Osborne. 1978. Changes in Rat Hepatic Cell Membranes
During 2,3,7,8-Tetrachlorodibenzo-p-dioxin Intoxication. In: Dioxin--
Toxicological and Chemical Aspects, F. Cattabeni, A. Cavallaro, and G.
Galli, eds., SP Medical and Scientific Books, New York, London.
Greig, J. B., D. M. Taylor, and J. D. Jones. 1974. Effects of TCDD on
Stimulated DNA Synthesis in the Liver and Kidney of the Rat. Chem. Biol.
Interactions, 8:31-39.
Greig, J. B., et al. 1973. Toxic Effects of 2,3,7,8-TCDD. Fd. Cosmet.
Toxicol., 11:585-595.
Gribble, W. G. 1974. TCDD, a Deadly Molecule. Chemistry, 47(2):15-18,
February.
Guenthner, T. M., and D. W. Nebert. 1977. Cytosolic Receptor for Aryl
Hydrocarbon Hydroxylase Induction by Polycyclic Aromatic Compounds. Biol.
Chem., 24:8981-89.
Guenthner, T. M., et al. 1979a. Evidence in Rat and Mouse Liver for
Temporal Control of Two Forms of Cytochrome P-450 Inducible by TCDD.
Environ. J. Biochem., 91(2):449-456.
Guenthner, T. M. , et al. 1979b. Microsomal Aryl Hydrocarbon Hydroxylase in
Rat Adrenal: Regulation by ACTH but not by Polycyclic Hydrocarbons. Mol.
Pharmacol., 15:719-728.
213
-------
Gupta, B. N. , et al. 1973. Pathologic Effects of 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin in Laboratory Animals. Environmental Health Perspectives,
5:125-140.
Gustafsson, J. A., and M. Ingelman-Sundberg. 1979. Changes in Steroid
Hormone Metabolism in Rat Liver Microsomes Following Administration of TCDD.
Biochemical Pharmacology, 28:497-499.
Gustafsson, J. , et al. 1979. Mechanisms Involved in Tissue Responsiveness
to Chemical Carcinogens and in Formation of Carcinogenic Metabolites from
Aromatic Hydrocarbons. Toxicology Research Projects Directory, 4:9.
Hanna, R. M., and D. R. Goldberg, n.d. Dioxin Monitoring Project: Final
Report, Region II c/o Rutgers University, U.S. EPA Files. Unpublished.
Hardell, L. 1979. Malignant Lymphoma of Histiocytic Type and Exposure to
Phenoxyacetic Acids or Chlorophenols. Lancet, 55-56, January 6.
Hardell, L. , and A. Sandstrom. 1978. Malignant Mesenchymal Soft-Tissue
Tumors and Exposure to Phenoxy Acid or Chlorophenols. A Case Control Study.
Lakartidringen, 75(49):3535-36.
Hardell, L. , et al. 1974. Case-Control Study of Soft-Tissue Sarcomas and
Exposure to Phenoxyacetic Acids of Chlorophenols. Br. J. Cancer,
39(6):711-717.
Harless, R. L. 1976. Presentation Given at TCDD Workshop, Universita Di
Milano, Institute Di Framacognosia. U.S. EPA Files. Unpublished.
Harless, R. L. 1980. Direct Testimony before the Administrator, U.S. EPA,
Re: FIFRA Docket Nos. 415 et al. EPA Exhibit No. 212. April 23.
Harris, M. W. , et al. 1973. General Biological Effects of TCDD in Lab
Animals. Environmental Health Perspectives, 5:101-109, September.
Harrison, D. D. , C. I. Miller, and R. C. Crews. 1979. Residual Levels of
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Near Herbicide Storage and
Loading Areas at Eglin AFB, Florida. AFATL-TR-79-20. February.
Harrison, W. S., A. T. Peters, and F. M. Rowe. 1943. Polyhalogeno-o-
anisidines and Their Derivatives. J. Am. Chem. Soc., pp. 235-237.
Haskelberg, L. 1947. The Halogenation of Aryloxyacetic Acids and Their
Homologs. J. Org. Chem., 12:426-433.
Hatfield, M. 0., (Senator). 1977. Written Communication to D. Costle, U.S.
EPA Administrator, November 3.
Hawley, G. 1971. Condensed Chemical Dictionary. 8th ed., Van-Nostrand
Reinhold Co., New York.
214
-------
Hay, A. 1976a. Toxic Cloud Over Seveso. Nature, 262:636-638, August 19.
Hay, A. 1976b. Seveso, The Problems Deepen. Nature, 264:309-310, November
18.
Hay, A. 1977a. Seveso Solitude. Nature, 267:384-385, June 2.
Hay, A. 1977b. Identifying Carcinogens. Nature, 269:468-470, October 6.
Hay, A. 1978a. Vietnam's Dioxin Problem. Nature, 271:597-598, London,
February 16.
Hay, A. 1978b. Company's Claim Sparks Fresh Controversy Over Seveso.
Nature, 247:108, July.
Helling, C. S. , et al. 1973. Chlorodioxins in Pesticides, Soils, and
Plants. J. Environ. Quality, 2(2):171-178.
Hepner, G. W. 1979. Detection of Carcinogen-Induced Stimulation of Cyto-
chrome P-448-Associated Enzymes by 14C02 Breath Analysis Studies Using
Dimethyl aminoazobenzene. Gastroenterology, 76(2):267-271.
Higgenbotham, G. R., et al. 1968. Chemical and Toxicological Evaluations
of Isolated and Synthetic Chloro. Derivatives of Dibenzo-p-dioxin. Nature,
220:702-703.
Highman, B. , T. B. Gaines, and J. J. Schumacher. Renal Alkaline Phosphatase
Activity in Fetal Offspring of Maternal Mice Given 2,4,5-Trichlorophenoxy-
acetic Acid. University of Arkansas College of Medicine, Little Rock,
Arkansas; and the National Center for Toxicological Research, Jefferson,
Arkansas.
Highman, B. , et al. 1977. Retarded Development of Fetal Renal Alkaline
Phosphatase in Mice Given 2,4,5-T. J. Toxicol. Environ. Health,
2:1007-1018.
Homberger, E., et al. 1979. The Seveso Accident: Its Nature, Extent and
Consequence. Givauden Research Company, Ltd. and F. Hoffman-LaRoche and
Co., Ltd. Confidential.
Hook, G. E. R. , J. K. Haseman, and G. W. Lucier. 1975. Induction and
Suppression of Hepatic and Extrahepatic Microsomal Foreign-Compound-
Metabolizing Enzyme Systems by 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Chem.
Biol. Interactions, 10:199-214.
Hook, G. E. R., et al. 1975. 2,3,7,8-TCDD Induced Changes in the Hydroxy-
lation of Biphenyl by Rat Liver Microsomes. Biochemical Pharmacology,
24:335-340.
Hook, J. B. , et al. 1978. Renal Effects of 2,3,7,8-TCDD. Environ. Sci.
Res., 12:381-8.
215
-------
Khera, K. S. , and W. P. McKinley. 1972. Pre- and Postnatal Studies on
2,4,5-Trichlorophenoxyacetic Acid, 2,4-Dichlorophenoxyacetic Acid and Their
Derivatives in Rats. Toxicol. Appl. Pharmacol., 22:14-28.
Khera, K. S. , and J. A. Ruddick. 1973. Polychlorodibenzo-p-dioxins Peri-
natal Effects and the Dominant Lethal Test in Wistar Rats. In: Chloro-
dioxins-Origin and Fate, E. H. Blair, ed. Advances in Chemistry, Series
120, American Chemical Society, Washington, D.C., pp. 70-84.
Kimble, B. J. , and M. L. Gross. 1980. Tetrachlorodibenzo-p-dioxin Quanti-
tation in Stack-Collected Coal Fly Ash. Science, 207:59-61, January 4.
Kimbrough, R. D. 1971. Review of the Toxicity of Hexachlorophene. Arch.
Environ. Health, 23:119-122.
Kimbrough, R. D. 1972. Toxicity of Chlorinated Hydrocarbons and Related
Compounds. Arch. Environ. Health, 25:125-131.
Kimbrough, R. D. 1974. The Toxicity of Polychlorinated Polycyclic Com-
pounds and Related Chemicals. CRC Critical Reviews in Toxicology,
2(4):445-498.
Kimbrough, R. D. 1976. Hexachlorophene: Toxicity and Use as an Anti-
bacterial Agent. Essays in Toxicology, 7:99-120.
Kimbrough, R. D. , et al. 1977. Epidemiology and Pathology of a Tetra-
chlorodibenzodioxin Poisoning Episode. Arch. Environ. Health, 32(2):77-86.
Kimmig, J. , and K. H. Schulz. 1957. Occupational Acne (Chloracne) Caused
by Chlorinated Aromatic Cyclic Ethers. Dermatologica, 115:540-546.
Kirsch, R. et al. 1975. Structural and Functional Studies of Ligandin, a
Major Renal Organic Anion-binding Protein. J. Clin. Invest. 55:1009-1019.
Kitchin, K. T. , and J. S. Woods. 1978. 2,3,7,8-TCDD Induction of Aryl
Hydrocarbon Hydroxylase in Female Rat Liver. Evidence for De Novo Synthesis
of Cytochrome P-448. Mol. Pharmacol., 19:890-99.
Kitchin, K. T. , et al. 1979. TCDD Effects on Hepatic Microsomal Cytochrome
p-448-Mediated. Toxicol. Appl. Pharmacol., 47(3): 537-546.
Klecka. G. M. , and D. T. Gibson. 1979. Metabolism of Dibenzo[l,4]dioxin by
a Pseudomonas Species. Biochem. J., 180:639-645.
Kluwe, W. M. 1978. Selective Modification of the Renal and Hepatic Toxic-
ities of Chloroform by Induction of Drug-Metabolizing Enzyme Systems in
Kidney and Liver. J. Pharmacol. Exp. Ther., 207(2):449-473.
Kocher, C. W. , et al. 1978. A Search for 2,3,7,8-Tetrachlorodibenzo-p-
Dioxin in Beef Fat. Bulletin of Environmental Contamination and Toxicology,
19:229-236.
Kociba, R. J. 1979. Toxicology Studies of TCDD in Rats. Dev. Toxicol.
Environ. Sci. , 281:7.
218
-------
Kociba, R. J. , et al. 1976. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)--
Results of a 13-Week Oral Toxicity Study in Rats. Toxicol. Appl.
Pharmacol., 35:553-574.
Kociba, R. J. , et al. 1978. Results of a Two Year Chronic Toxicity and
Oncogenicity Study of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Rats. Toxicol.
Appl. Pharmacol., 46(2):279-304.
Kouri, R. E. , et al. 1978. 2,3,7,8-Tetrachlorodibenzo-p-dioxin as Cocar-
cinogen Causing 3-Methylcholanthrene-im'tiated Subcutaneous Tumors in Mice
Genetically "Nonresponsive" at Ah Locus. Cancer Research, 38:2777-2783,
September.
Kozak, V. P., et al. 1979. Reviews of the Environmental Effects of Pollu-
tants: XI. Chlorophenols. ORNL/EIS-128, EPA-600/1-79-012, pp. 464-5.
Kupfer, D. 1975. Effects of Pesticides and Related Compounds on Steroid
Metabolism and Function. CRC Critical Reviews in Toxicology, 4(1):83-124,
October.
Lancet. 1976. Seveso. 2(7980):297, August 7.
Lancet. 1977. Long-term Effects of Dioxin Exposure. 1:8014, April 2.
Langer, H. G., T. P. Brady, and P. R. Briggs. 1973. Formation of Dibenzo-
dioxins and Other Condensation Products From Chlorinated Phenols, and Deri-
vatives. Environmental Health Perspectives. 5:3-9, September.
Langer, H. G., et al. 1973. Thermal Chemistry of Chlorinated Phenols. In:
Chlorodioxins-Origin and Fate, E. Blair, ed. Advances in Chemistry, Series
120, American Chemical Society, Washington, D.C. , pp. 26-32.
Laporte, J. R. 1977. Effects of Dioxin Exposure. Lancet, II 8028:82-83,
July 9.
Lawless, E. W. , T. L. Ferguson, and A. F. Meiners. 1975. Guidelines for
the Disposal of Small Quantities of Unused Pesticides. EPA-670/2-75-057.
Lawrence Eagle Tribune. 1978. Tot, 3, May Be Vietnam War Casualty.
October 30, pp. A-l, A-16.
Leng, M. L. 1976. Comparative Metabolism of Phenoxy Herbicides in Animals.
In: Fate of Pesticides in Large Animals, G. W. Ivie and H. W. Dorough, eds.
Academic Press, New York. pp. 53-76.
Leng, M. L. 1977. Are Lawn Weed Killers Really Hazardous. Dow Chemical
U.S.A. Report, August 29.
Liberti, A. 1978. Field Photodegradation of TCDD by Ultraviolet Radia-
tions. In: Dioxin—Toxicological and Chemical Aspects, F. Cattabeni, A.
Cavallaro, and G. Galli, eds., SP Medical and Scientific Books, New York,
London.
219
-------
Lira, P., M.D. 1978. Velsicol Corp., personal communication, August 29.
Lucier, G. W. 1979. Developmental Toxicology of the Halogenated Aromatics:
Effects on Enzyme Development. Ann. New York Acad. Sci., 320:449-457.
Lucier, G. W., et al. 1973. TCDD-Induced Changes in Rat Liver Microsomal
Enzymes. Environmental Health Perspectives, 5:199-209, September.
Lucier, G. W., et al. 1979. Laboratory Studies on the Immune Effects of
Halogenated Aromatics. Ann. New York Acad. Sci., 320:473-486.
Lucier, G. W. , 0. S. McDaniel, and G. E. R. Hook. 1975. Nature of the
Enhancement of Hepatic Uridine Diphosphate Glucuronyl-transferase Activity
by 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Rats. Biochem. Pharmacol.
24:325-334.
Luster, M. I. 1979a. Effects of Brief In Vitro Exposure to TCDD on Mouse
Lymphocytes. J. Environ. Pathol. Toxicol., 2(4):965-977.
Luster, M. I. 1979b. Immunochemistry of Dioxin Action on the Lymphocyte.
Tox. Research Proj. Directory, 04:06.
Luster, M. I., et al. 1978. Inability of Passive Antibodies to Reverse the
Effects of Dioxin Toxicity. Chemosphere, 7(1):29-34.
Madge, D. S. 1977. Effects of Trichlorophen Oxyacetic Acid and Chloro-
dioxins on Small Intestinal Function. Gen. Pharmacol., 8(5-6):319-29.
Madhukar, B. V., et al. 1979a. Comparison of Induction Patterns of Rat
Microsomal Mixed-Function Oxidases by Pesticides and Related Chemicals.
Pestic. Biochem. Physiol., 11:301-308.
Madhukar, B. V., et al. 1979b. Depression of ATPase Activity in Hepatocyte
Surface Membranes of Rats by 2,3,7,8-TCDD Treatment. Toxicol. Appl.
Pharmacol., 48(1):A152.
Manis, J. 1977. Induction of Intestinal From Transport by 2,3,7,8-TCDD, an
Environmental Pollutant and Potent Inducer of Aryl Hydrocarbon Hydroxylase.
Clin. Res., 25(3):468A.
Manis, J. 1979. Intestinal Organic Anion Transport, Glutathione
Transferase and Aryl Hydrocarbon Hydroxylase Activity: Effect of Dioxin.
Life Sci., 24:1373-1380.
Manis, J., and G. Kim. 1979. Stimulation of Iron Absorption by
Polychlorinated Aromatic Hydrocarbons. Am. J. Physiol., 236: E763-E768.
March, J. 1968. Advanced Organic Chemistry: Reactions, Mechanisms, and
Structure. McGraw-Hill Book Co., New York, pp. 519-520.
220
-------
Marselos, M. 1979. Comparison of Phenobarbital and Carcinogen-Induced
Aldehyde Dehydrogenases in the Rat. Biochem. Biophys. ACTA, 583(1):110-110.
Marselos, M. , et al. 1978. Responses of the D-Gluccionic Acid Pathway in
Rat Tissues to Treatment with TCDD. Xenobiotica, 8(7):397-402.
Matsumura, F., and H. J. Benezet. 1973. Studies on the Bio-accumulation
and Microbial Degradation of 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Environ-
mental Health Perspectives, 5:253-258, September.
Mauk, C. E. , H. W. Prengle, Jr., and J. E. Payne. 1976. Oxidation of
Pesticides by Ozone and Ultraviolet Light, U.S. Army Mobility Equipment
Research and Development Command, AD-A028 306/9ST.
May, G. 1973. Chloracne From the Accidental Production of Tetrachloro-
dibenzodioxin. British J. Industrial Medicine, 30:276-283.
McCann, J., et al. 1976. Detection of Carcinogens as Mutagens in the
Salmonella/Microsome Test: Assay of 300 Chemicals. Proc. Nat. Acad. Sci.
73:950-954.
McConnell, E. E., and J. A. Moore. 1976. The Comparative Toxicity of
Chlorinated Dibenzo-p-dioxin Isomers in Mice and Guinea Pigs. Toxicol.
Appl.' Pharmacol. , 37:146.
McConnell, E. E. , J. A. Moore, and D. W. Dalgard. 1978. Toxicity of
2,3,7,8-Tetrachlorodibenzo-p-dioxin in Rhesus Monkeys (Macaca Mulatta)
Following a Single Oral Dose. Toxicol. Appl. Pharmacol., 43:175-187.
McConnell, E. E., et al. 1978. The Comparative Toxicity of Chlorinated
Dibenzo-p-dioxins in Mice and Guinea Pigs. Toxicol. Appl. Pharmacol.,
44:335-356.
Mclnty, L. 1976. The Graveyard on Milan's Doorstep. New Science,
71 (104)-.383-385.
Mclntyre, T. J. (Senator). 1970. Herbicide Program in Vietnam. Congres-
sional Record, August 25, pp. 29932-30012.
McNulty, W. P., M.D. 1978a. Written communication to U.S. EPA Office of
Pesticide Programs, July 27.
McNulty, W. P., M.D., 1978b. Oregon Regional Primate Research Center,
personal communication, August 8.
McNulty, W. P., et al. 1979a. PCB and TCDD Orofacial Teratogenesis in
Macaca Mulatta. Toxicology Research Projects Directory, 04:101.
McNulty, W. P., et al. 1979b. Toxicity of TCDD for Rhesus Monkeys: Brief
Report. Pub. No. 878, Oregon Primate Research Center.
221
-------
McQueen, E. G. , et al. 1977. 2,4,5-T and Human Birth Defects, New Zealand
Department of Health, June.
Mercier, M. J. 1976. 2,3,7,8-Tetrachlorodibenzo-p-dioxin: An Overview.
In: Proceedings of the Expert Meeting on the Problems Raised by TCDD
Pollution, A. Berlin, A. Buratta, and M. T. Van der Venne, eds. Milan. In
press.
Merck Index. 1978. 9th ed. , M. Windholz, ed. Merck & co., Inc., Rahway,
New Jersey.
Merenda, J. J. 1979. TSCA Section 8(e) submission on Polychlorinated
Dibenzo-p-dioxins (PCDD's). Letters and enclosures to E. Blair, vice
president Dow Chemical Co., from Director, Assessment Division, EPA. EPA
Document Control No. 8EHQ-1178-0209, February 15.
Meselson, M. , P. W. O'Keefe, and R. Baughman. 1978. The Evaluation of
Possible Health Hazards From TCDD in the Environment. Presentation for
Symposium on the Use of Herbicides in Forestry. Arlington, Virginia,
February 21-22.
Miller, S. 1979. Source of Dioxins. Chemical and Engineering News. March
12, p. 4.
Miller, R. A., L. A. Norris, and C. L. Hawkes. 1973. Toxicity of 2,3,7,8-
TCDD in Aquatic Organisms. Environmental Health Perspectives, 5:177-187,
September.
Milnes, M. H. 1971. Formation of 2,3,7,8-Tetrachlorodibenzodioxin by
Thermal Decomposition of Sodium 2,4,5-Trichlorophenate. Nature (London),
232:395-396, August 6.
Mitchell, L. C. 1961. The Effect of Ultraviolet Light on 141 Pesticide
Chemicals. J. Assoc. Offic. Agr. Chem., 44:643-712.
MITRE Corporation. 1977. The Analysis of Existing Wood Preserving Tech-
niques and Possible Alternatives. Technical Report 7520. Prepared for U.S.
EPA, Contract No. 68-01-4310.
Model!, J., R. P. deFilippi, and V. Krukonis. 1978. Regeneration of Acti-
vated Carbon With Supercritical Carbon Dioxide. Presented at the ACS Con-
ference, Miami, Florida. September 14.
Moore, J. A. 1979. A Pesticide. Science, 203(4382):741-742. February 23.
Moore, J. A., and R. E. Faith. 1976. Immunologic Response and Factors
Affecting its Assessment. Environmental Health Perspectives, 18:125-132.
Moore, J. A., B. N. Gupta, and J. G. Vos. 1976. Toxicity of 2,3,7,8-Tetra-
chlorodibenzofuran—Preliminary Results. In: National Conference on Poly-
chlorinated Biphenyls, Chicago, 1975. EPA-560/6-75-004.
222
-------
Moore, J. A., M. W. Harris, and P. W. Albro. 1978. Tissue Distribution of
(14C) Tetrachlorodibenzo-p-Dioxin in Pregnant and Neonatal Rats. National
Institute of Environmental Health Sciences, Research Triangle Park, North
Carolina.
Moore, J. A., et al. 1973. Postnatal Effects of Maternal Exposure to
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Environmental Health Perspec-
tives, 5:81-85.
Moye, A. L. 1972. Experiencing Relevancy in Organic Chemistry. Hexa-
chlorophene: The Great Clean-All. Journal of Chemical Education,
49(11):770-771, November.
Murray, F. J. , et al. 1978. Three-Generation Reproduction Study of Rats
Ingesting TCDD. Toxicol. Appl. Pharmacol., 41:200-201.
Nagayama, J. , M. Kuratsune, and Y. Masuda. 1976. Determination of Chlo-
rinated Dibenzofurans in Kanechlors and "Vusho Oil." Bulletin of Environ-
mental Contamination and Toxicology, 15:9-13.
Nash, R. G. , and M. L. Beall, Jr. 1977. Environmental Distribution of
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Applied With Silvex to Turf in
Microagroecosystem. Final Report. U.S. EPA-USDA Interagency Agreement,
EPA-1AG-D6-0054, ARS 173, EPA No. 1001-704.
Nash, R. G. , and M. L. Beall, Jr. 1978. A Microagroecosystem to Monitor
the Environmental Fate of Pesticides. Pesticide Degradation Laboratory,
ARS, USDA, Beltsville, Maryland. Unpublished.
National Academy of Sciences. 1974. Committee on the Effects of Herbicides
in South Vietnam, Part A. Summary and Conclusions. Washington, D.C.
National Academy of Sciences. 1977. Drinking Water and Health. Part II,
Chapter VI and Bibliography.
Nature. 1970. Another Herbicide on the Blacklist. Vol. 226:309-311.
London.
Neal, R. A. 1979. Mechanisms of Toxicity of the Chlorinated p-Dioxins.
Toxicology Research Projects Directory, 04:11.
Nebert, D. W. , S. S. Thorgeirsson, and J. S. Felton. 1976. Genetic
Differences in Mutagenesis, Carcinogenesis, and Drug Toxicity. In: In
Vitro Metabolic Activation in Mutagenesis Testing, F. J. deSerrers, et al.,
ed. Elsevier/North Holland Publishing Co., Amsterdam, 105-124.
Nelson, C. J. , et al. 1979. Retrospective Study of the Relationship
Between Agricultural Use of 2,4,5-T and Cleft Palate Occurrence in Arkansas.
Teratology, 19:377-384.
Nelson, G. (Senator). 1973. Statement on Dioxins. Congressional Record,
January 17.
223
-------
Nelson, J. D., et al. 1977. 2,3,7,8-Tetrachlorodibenzo-p-dioxin In Vitro
Binding to Rat Liver Microsomes. Bulletin of Environmental Contaminants and
Toxicology, 18(1):9-13.
Neubert, D. , and I. Dillmann. 1972. Embryotoxic Effects in Mice Treated
With 2,4,5-Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzo-p-
dioxin. Naunyn-Schmiedeberg1s Arch. Exp. Path. Pharmacol, 272:243-264.
Neubert, D. , et al. 1973. A Survey of the Embryotoxic Effects of TCDD in
Mammalian Species. Environmental Health Perspectives, 5:67-79.
Newton, M. , and S. Snyder. 1978. Exposure of Forest Herbivores to
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in Areas Sprayed With 2,4,5-T.
Bulletin of Environmental Contamination and Toxicology, 20(6):743-750.
Nilsson, C. A., et al. 1974. Chromatographic Evidence for the Formation of
Chlorodioxins From Chloro-2-Phenoxyphenols. J. Chromatography, 96:137-147.
Niwa, A., et al. 1975. Genetic Expression of Aryl Hydrocarbon Hydroxylase
Activity in the Mouse. Archives of Biochemistry and Biophysics,
166:559-564.
Nolan, R. J. , et al. 1979. Elimination of Tissue Distribution of TCDD in
Female Guinea Pigs Following a Single Oral Dose. Toxicol. Appl. Pharmacol.,
48(1):A162.
Norback, D. H. 1975. Tissue Distribution and Excretion of Octachloro-
dibenzo-p-Dioxin in the Rat. Toxicol. Appl. Pharmacol., 32:330-338.
Norback, D. H. , and J. R. Allen. 1973. Biological Responses of the Non-
human Primate, Chicken and Rat to Chlorinated Dibenzo-p-dioxin Ingestion.
Environmental Health Perspectives, 5:233-240.
Norman, R. L. 1978. Identification of the Major Cytochrome P-450 Form
Transplacentally Induced in Neonatal Rabbits by 2,3,7,8-Tetrachlorodibenzo-
p-dioxin. J. Biol. Chem., 253(23):8640-8647.
Oberacker, D. A., and S. Lees. 1977. Microwave Plasma Detoxification of
Hazardous and Toxic Materials. In: News of Environmental Research in
Cincinnati. U.S. EPA, Municipal Environmental Research Laboratory.
Occupational Safety and Health Reporter. 1979. Health Hazards: NIOSH
Begins Epidemiological Study of All Workers Exposed to Dioxin TCDD. Vol. 9,
No. 26, November 29.
Offut, C. 1978. EPA Office of Toxic Substances, personal communication,
September 8.
Oishi, S., M. Morita, and H. Fukuda. 1978. Comparative Toxicity of Poly-
chlorinated Biphenyls and Dibenzofurans in Rats. Toxicol. Appl. Pharmacol.,
43:13-22.
224
-------
01ie, L., P. L. Vermeulen, and 0. Hutzinger. 1977. Chlorodibenzo-p-Dioxins
and Chlorodibenzofurans Are Trace Components of Fly Ash and Flue Gas of Some
Municipal Incinerators in the Netherlands. Chemosphere, 8:455-459.
Oliver, R. J. 1975. Toxic Effects of 2,3,7,8-Tetrachlorodibenzo 1,4 Dioxin
in Laboratory Workers. British J. of Industrial Medicine, 32:49-53.
Ott, P., M.D. 1978. EPA, personal communication, August 29.
Ottinger, R. S. , et al. 1973. Recommended Methods of Reduction, Neutrali-
zation, Recovery, or Disposal of Hazardous Waste. Volume 3. NTIS PB-224
582.
Parkki, M. G. , and A. Aitio. 1978. Induction of Drug Metabolizing Enzymes
in Different Rat Tissues by TCDD. Arch. Toxicol. ISS Supl. 1, 261-5.
Parks, M. 1978. The Seveso Case. EPA Journal, 4(8):11-15, 35, September.
Peracchio, A. 1979. Dow Chemical Faces Suits From Veterans of Vietnam Over
Babies With Defects. Newsday, copyright.
Peterson, J. 1978. Seveso: The Event. Ambio, 7(5-6):232-233.
Physi'cians1 Desk Reference. 1978. 32nd edition. Medical Economics
Company, Oradell, New Jersey.
Piper, W. N. 1979. Toxicant Deregulation of Endocrine Heme Biosynthesis.
Toxicology Research Projects Directory, 04:06.
Piper, W. N., J. Q. Rose, and P. J. Gehring. 1973. Excretion and Tissue
Distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Rat. Environ-
mental Health Perspectives, 5:241-244.
Plimmer, J. R. 1972. Principles of Photodecomposition of Pesticides:
Degradation of Synthetic Organic Molecules in the Biosphere. National
Academy of Sciences, Washington, D.C.
Plimmer, J. R. 1973. Technical Pentachlorophenol: Origin and Analysis of
Base-Insoluble Contaminants. Environmental Health Perspectives, 5:41-47.
Plimmer, J. R. 1978a. Approaches to Decontamination or Disposal of Pesti-
cides: Photodecomposition. In: Disposal and Decontamination of Pesti-
cides, M. V. Kennedy, ed. ACS Symposium Series 73, American Chemical
Society, Washington, D.C., pp. 12-23.
Plimmer, J. R. 1978b. Photolysis of TCDD and Trifluralin on Silica and
Soil. Bulletin of Environmental Contamination and Toxicology, 20:87-92.
Plimmer, J. R., et al. 1973. Photochemistry of Dibenzo-p-dioxins. In:
Chlorodioxins—Origin and Fate, E. Blair, ed. Advances in Chemistry, Series
201, American Chemical Society, Washington, D.C., pp. 44-54.
225
-------
Pocchiari, F. 1978. 2,3,7,8-Tetrachlorodibenzo-p-para-dioxin Decontamina-
tion. In: Chlorinated Phenoxy Acids and Their Dioxins, C. Ramel, ed.
Ecol. Bull. (Stockholm), 27:67-70.
Pocchiari, F. , V. Silano, and A. Zampieri. 1979. Human Health Effects from
Accidental Release of TCDD at Seveso, Italy. Ann. New York Acad. Sci.,
311:20.
Pohland, A. E. , and G. C. Yang. 1972. Preparation and Characterization of
Chlorinated Dibenzo-p-dioxin. J. Agric. Food Chem., 20:1093-1099.
Pohland, A. E. , G. C. Yang, and N. Brown. 1973. Analytical and Confirma-
tive Techniques for Dibenzo-p-dioxins Based upon their Cation Radicals.
Environmental Health Perspectives, 5:9-13.
Pokorny, R. 1941. Some Chlorophenoxyacetic Acids, J. Am. Chem. Soc.,
63:1768.
Poland, A. 1973. Chlorinated Dibenzo-p-Dioxins: Potent Inducer of
a-Aminolevulinic Acid Synthetase and Aryl Hydrocarbon Hydroxylase 11. A
Study of the Structure-Activity Relationship. Mol. Pharmacol., 9:736-747.
Poland, A., and E. Glover. 1974. Comparison of 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin, A Potent Inducer of Aryl Hydrocarbon Hydroxylase, With
3-Methyl Chloranthrene. Mol. Pharmacol., 10:349-359.
Poland, A., and A. Kende. 1976. 2,3,7,8-Tetrachlorodibenzo-p-dioxin:
Environmental Contaminant and Molecular Probe. Federal Proceedings,
35(12):2404-2411.
Poland, A., et al. 1971. A Health Survey of Workers in a 2,4-D and 2,4,5-T
Plant With Special Attention to Chloracne, Porphyria Cutanea Tarda, and
Psychologic Parameters. Arch. Environ. Health, 22:316-327.
Poland, A., et al. 1976. 3,4,3,,4,-Tetrachloro Azoxybenzene and Axoben-
zene: Potent Inducers of Arylhydrocarbon hydroxylase. Science, 194:627.
Poole, C. 1979. U.S. EPA, personal communication.
Purkyne, J. E. , et al. 1974. Acne Chlorina Porphyria Cutanea Tarda A Jine
Projevy Celkoue Intoxikace Pki Uyrobe Herbicid. Ceskoslovenska
Dermatologie, 3(49):145-57.
Ramsey, J. C. 1979. The In Vivo Biotransformation of TCDD in the Rat.
Toxicol. Appl. Pharmacol., 48(1):A162.
Rappe, C. 1978. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Introduction.
In: Dioxin—Toxicological and Chemical Aspects, F. Cattabeni, A. Cavallaro,
and G. Galli, eds. SP Medical and Scientific Books, New York, London, pp.
9-11.
226
-------
Rappe, C. 1979. Polychlorinated Dibenzodioxins and Dibenzofuran Compounds
of Current Interest. Lakartidrigen, 76(l-2):21-29.
Rappe, C. , et al. 1978. Formation of Polychlorinated Dibenzo-p-dioxins
(PCDDs) and Dibenzofurans (PCDFs) by Burning or Heating Chlorophenates.
Chemosphere, 7(3):269-281.
Rawls, R. 1979. Dow Finds Support, Doubt for Dioxin Ideas. Chemical and
Engineering News, pp. 23-29, February 12.
Reece, M. 1978a. EPA, personal communication, September 18.
Reece, M. 1978b. Written communication from U.S. EPA Pesticide Programs-,
October 10.
Reece, M. 1978c. EPA, personal communication, November 2.
Reggiani, G. 1977. Medical Problems Raised by the TCDD Contamination in
Seveso, Italy. Presented at the 5th International Conference on Occupa-
tional Health in the Chemical Industry (Medichem), San Francisco, September
5-10.
Reggiani, G. 1978. Medical Problems Raised by the TCDD Contamination in
Seveso, Italy. Arch Toxicol., 40(3):161-188.
Reggiani, G. 1979a. Estimation of the TCDD Toxic Potential in the Light of
the Seveso Accident. Arch. Toxicol. (Suppl), 291-302.
Reggiani, G. 1979b. TCDD Contamination in Italy: The Risk Assessment of
Low-Level Exposure, Cumulative Effect and Long-Term Consequences. Toxicol.
Appl. Pharmacol., 48(1):A180.
Revzin, P. 1979. Chemical Cloud Still Casts Long Shadow Over Seveso, Italy.
The Wall Street Journal, July 10.
Richards, B. 1979a. Pesticide Waste Dumping Probed Near Little Rock. The
Washington Post. May 19.
Richards, B. 1979b. Arkansas Pesticide Plant Being Investigated. The
Washington Post. June 17.
Richards, B. 1979c. Arkansas Site May Hold Clue. The Washington Post.
July 25.
Riley, B. T. 1975. Summation of Conditions and Investigations for the
Complete Combustion of Organic Pesticides. U.S. Environmental Research
Laboratory, EPA-600/2-75-044.
Robbins, A. 1979. Dioxin Studies. Science, Vol. 205, September 28, p.
1332.
227
-------
Rogers, C. J., and R. Allen. 1978. Developing Technology for Detoxifica-
tion of Pesticides and Other Hazardous Materials. In: Disposal and Decon-
tamination of Pesticides, M. V. Kennedy, ed. ACS Symposium, Series 73,
American Chemical Society, Washington, D.C.
Roper, M. , T. Stack, and R. A. Deitrich. 1976. Phenobarbital and Tetra-
chlorodibenzo-p-dioxin Induce Different Isoenzymes of Aldehyde Dehydro-
genase. Fed. Proc. 35:282.
Rose, J. Q. , et al. 1976. The Fate of 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Following Single and Repeated Oral Doses to the Rat. Toxicol. Appl.
Pharmacol., 36:209-226.
Rosen, J. D. 1971. Photodecomposition of Organic Pesticides. In: Organic
Compounds in Aquatic Environments, S. J. Faust and J. V. Hunter, eds. Marcel
Dekker, Inc., New York.
Saint-Ruf, G. 1978. The Structure and Biochemical Effects of TCDD. In:
Dioxin--Toxicological and Chemical Aspects, F. Cattabeni, A. Cavallaro, and
G. Galli, eds. SP Medical and Scientific Books, New York, London.
Saint-Ruf, G., and Do-PhuocHien. 1975. Similarity of the Biochemical
Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and the 2,3,7,8-Tetrabromo-
dibenzo-p-dioxin in the Rat. C. R. Hebd. Seances Acad. Sci. Paris Ser. D,
280(23):2709-2711.
Salkinoja-Salonen, M. 1979a. Waste Purifying Procedure. U.S. Patent No.
4,169,049, September 25.
Salkinoja-Salonen, M. 1979b. Microbial Dechlorination of Chloro-Organics.
University of Helsinki, Finland. Presentation given at U.S. EPA offices,
IERL, Cincinnati, December 11.
Schantz, S. L., et al. 1979. Toxicological Effects Produced in Nonhuman
Primates Chronically Exposed to Fifty Parts Per Trillion 2,3,7,8-TCDD.
Toxicol. Appl. Pharmacol., 48(1):A180.
Schwetz, B. A., P. J. Gehring, and R. J. Kociba. 1978. Toxicological
Properties of Pentachlorophenol Relative to its Content of Chlorinated
Dibenzo-p-Dioxins. Dow Chemical, Midland, Michigan.
Schwetz, B. A., P. A. Keeler, and P. J. Gehring. 1973. The Effect of
Purified and Commercial Grade Pentachlorophenol on Rat Embryonal and Fetal
Development. Toxicol. Appl. Pharmacol., 28:146-150.
Schwetz, B. A., et al. 1973. Toxicology of Chlorinated Dibenzo-p-dioxins.
Environmental Health Perspectives, 5:87-99.
Science. 1979. Agent Orange Furor Continues to Build. Vol. 205, August
24.
228
-------
Sconce, J. S., ed. 1967. Chlorine: Its Manufacture, Properties and Uses.
Reinhold Publishing Corp., New York, pp. 448-456, and 851-852.
Scurlock, A. C., et al. 1975. Incineration in Hazardous Waste Management.
U.S. Environmental Protection Agency, NTIS PB-261 049.
Seefeld, M. D., et al. 1979a. Effects of TCDD on Liver Function in Rats,
Rabbits and Guinea Pigs. Toxicol. Appl. Pharmacol., 48(1):A153.
Seefeld, M. D. , et al. 1979b. Time Course of TCDD Effects on Liver Func-
tion in Rhesus Monkeys. Toxicol. Appl. Pharmacol., 48(1):A160.
Seiler, J. P. 1973. A Survey on the Mutagenicity of Various Pesticides.
Experientia, 29(5):622-623.
Seiler, J. P. 1977. Inhibition of Testicular DNA Synthesis by Chemical
Mutagens and Carcinogens. Preliminary Results in the Validation of a Navel
Short Term Test. Mutation Res., 46:305-310.
Severe, R. 1979. Agent Orange, A Legacy of Suspicion. The New York Times,
May 27-29.
Shadoff, L. A., et al. 1977. The Gas Chromatographic - Mass Spectrometric
Determination of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Fat From Cattle Fed
Ronnel Insecticide. Ann. Chim., 67:583-592.
Sharma, R. P. 1978. Reversal of Immunologic and Toxicologic Effects of a
Single Exposure of TCDD in Mice. Trace Subst. Environ. Health, 12:299-306.
Shea, K. P., and B. Lindler. 1975. Pandora and the Storage Tank. Environ-
ment, 17(6):12-15, September.
Shiroishi, K. 1978. EPA Office of Enforcement, personal communication,
September 12.
Shiver, J. K. 1976. Converting Chlorohydrocarbon Wastes by Chlorolysis,
EPA-600/2-76-270.
Short, F. W., and E. F. Elslager. 1962. Intestinal Anthelmintics. I. The
Preparation of Bis (2,4,5-Trichlorophenol)--Piperazine Salt (Trichlofenol
Piperazine) and Other Phenol-Piperazine Salts. J. Med. Pharm. Chem., 5:642.
Sidwell, A. E. 1976a. Chemistry of 2,4,5-T Production, and History of
Trichlorophenol and 2,4,5-T Acid Manufacturers at Jacksonville, Arkansas.
Written communications to the Arkansas Dept. of Pollution Control and
Ecology, from Transvaal Inc., Jacksonville, Arkansas, September 17.
Sidwell, A. E. 1976b. TCDD Content of Soil and Liquid Sample. Written
communication to T. Bennett, Jr., Transvaal, Inc., from Transvaal, Inc.,
October 27.
229
-------
Sittig, M. 1969. Organic Chemical Process Encyclopedia, 2d ed. Noyes
Development Corp., Park Ridge, New Jersey.
Sittig, M., 1974. Pollution Control In the Organic Chemical Industry.
Noyes Data Corporation, Park Ridge, New Jersey, pp. 116-119.
Smith, F. A., B. A. Schwetz, and K. D. Nitchke. 1976. Teratogenicity of
2,3,7,8-Tetrachlorodibenzo-p-dioxin in CF-1 Mice. Toxicol. Appl.
Pharmacol., 38:517-523.
Solch, J. G. et al. 1978. The Analysis of Environmental Samples for
2,3,7,8-TCDD Utilizing High and Low Resolution Gas-Liquid
Chromatogrpahy-Mass Spectrometry. Final Report. U.S. EPA Contract No.
68-01-1959. June.
Solch, J. G. et al. 1980. Wright State University Quarterly Report to the
U.S. EPA on Cooperative Agreement No. CR 806846-01. March 23.
Sparschu, G. L., F. L. Dunn, and V. K. Rowe. 1970. Teratogenic Study of
2,3,7,8-fetrachlorodibenzo-p-dioxin in the Rat. Toxicol. Appl. Pharmacol.,
17:317-318.
Sparschu, G. L., F. L. Dunn, and V. K. Rowe. 1971. Study of the Terato-
genicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Rat. Fd. Cosmet.
Toxicol., 9:405-412.
Stanford Research Institute. 1976-1979. Directory of Chemical Producers,
USA. Menlo Park, California.
Stark, H. E. , J. K. McBride, and G. F. Orr. 1975. Soil Incorporation/
Biodegradation of Herbicide Orange. Vol. I. Microbial and Baseline Ecolog-
ical Study of the U.S. Air Force Logistics Command Test Range, Hill Air
Force Base, Utah. Final Report.
Stehl, R. H. , and L. L. Lamparski. 1977. Combustion of Several 2,4,5-T
Compounds: Formation of 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Science,
197:1008-1009.
Stehl, R. H. , et al. 1973. The Stability of Pentachlorophenol and Chlo-
rinated Dioxin to Sunlight, Heat and Combustion. In: Chlorodioxin—Origin
and Fate, E. H. Blair, ed. Advances in Chemistry, Series 120, American
Chemical Society, Washington, D.C. , pp. 119-125.
Storherr, R. W., et al. 1971. Steam Distillation Technique for the Anal-
ysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Technical 2,4,5-T. J. Assoc.
Off. Anal. Chem., 54:218-219.
Strigini, P. and A. Torriani. 1977. Seveso: "Encouraging Evidence"?
Science. 197:1034, 1036, September 9.
Sugar, J. 1979. Research Related to the Herbicide Buvinol, Especially for
Possible Carcinogenicity. TARC Sci. Publ., 25:167-172.
230
-------
Sugar, J. , et al. 1979. Role of Pesticides in Hepatocarcinogenesis. J.
Toxicol. Environ. Health, 5:1552-3, pp. 183-191.
Sweeney, G. D. 1979. Iron Deficiency Prevents Liver Toxicity TCDD.
Science, 204(4390):332-335.
Taylor, J. S. 1974. Chloracne—A Continuing Problem. Cutis, 13(585):4174.
Taylor, M. L. and T. 0. Tiernan. 1979. Written communication to L. Barnes,
American Public Health Association, Washington, D. C. 20036. April 4.
Taylor, M. 1980. Personal communication. The Brehm Laboratory, Wright
State University, March 4.
Techini, M. L., et al. 1977. Approaches to Examination of Genetic Damage
After a Major Hazard in Chemical Industry: Preliminary Cytogenetic Findings
on TCDD-exposed Subjects After Seveso Accident. Presented at the Expert
Conference on Genetic Damage Caused by Environmental Factors, Oslo, Norway,
May 11-13.
Tenzer, R. , et al. Characteristics of the Mobile Field Use System for the
Detoxification/Incineration of Residuals From Oil and Hazardous Material
Spill Clean-up Operations. Prepared for U.S. Environmental Protection
Agency by MBA Associates under Contract No. 68-03-2515.
Theiss, A. M. , and P. Goldman. 1977. Uber das Trichlorphenol-Dioxin-
Umfall-geschehen urn der BASF AG VOM 13 November 1953. In: Vortrag auf dem
IV Medichem-Kongress, Haifa, 1976. International Agency for Research on
Cancer.
Thigpen, J. E. , et al. 1975. Increased Susceptibility to Bacterial Infec-
tion as a Sequela of Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
Infection and Immunity, 12:1319-1324.
Thomas, P. T. , and R. Hinsdill. 1979. The Effect of Perinatal Exposure to
TCDD on the Immune Response of Young Mice. Drug. Chem. Tox. 2 Iss., 1-
2:77-98.
Tiernan, T. 0. 1975. Analytical and Chemical Support for Herbicide Dispo-
sition Activities. Final Report. U.S. Air Force Contract No.
F41608-76-C-0464.
Tiernan, T. 0. 1976. The Analysis of Environmental Samples for
2,3,7,8-Tetrachlorodibenzo-p-dioxin Utilizing High and Low Resolution Gas-
Liquid Chromatography-Mas Spectrometry. Final Report. U.S. EPA Contract
No. 68-01-1959.
Tiernan, T. 0. and M. L. Taylor. 1978. Development and Application of
Analytical Methodology for Determination of Hexa-, Hepta-, and Octachloro-
dibenzodioxins in Beef Samples. Final Report. USDA Contract No.
12-64-4-378.
Tiernan, T. 0. and M. L. Taylor. 1980. Interim Report on EPA Order No.
D2832NAEX. March 31.
231
-------
Tiernan, T. 0. et al. 1979. Determination of Tetrachlorodibenzo-p-dioxin
(TCDD) in Stack Effluent Samples Obtained During At-Sea Incineration of
Herbicide Orange. U.S. EPA Purchase Order No. DA-8-6414J. May 31.
Tiernan, T. 0. et al. 1980. Analyses of Industrial Samples for
Tetrachlorodibenzo-p-dioxins (TCDDs). Final Report. U.S. EPA Contract No.
68-03-2830 and Order Nos. 9T-1501-NTEX and OT-0267-NAEX. April 1.
Tiernan, T. 0. and M. L. Taylor. 1978. Development and Application of
Analytical Methodology for Determination of Hexa-, Hepta-, and Octachloro-
dibenzodioxins in Beef Samples. Final Report. USDA Contract No.
12-64-4-378. April.
Ton That, T. , et al. 1973. LeCancer Primaire du foie au Viet-nam Chirurgie
International Agency for Research on Cancer, 99:427-436.
Toth, K. , et al 1977. Carcinogenic Bioassay of the Herbicide
2,4,5-Trichlorophenoxy Ethanol (TCPE) With Different 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin (Dioxin) Content in Swiss Mice. In: International Con-
ference on Ecological Perspectives on Carcinogens and Cancer Control, Basel
and Karger, eds., Cremona, 1976.
Toth, K., et al. 1979. Careinogenicity Testing of Herbicide 2,4,5-T
Ethanol Containing Dioxin and of Pure Dioxin in Swiss Mice. Nature,
278(5704):548-549.
Toxic Materials News. 1979a. Toxic Materials News in Brief. 6(9):70,
February 28.
Toxic Materials News. 1979b. Remaining Uses of 2,4,5-T, Silvex Undergo
Review Prior to Possible Cancellation. July 18, p. 230.
Toxic Materials News. 1979c. Toxic Materials News In Brief. July 25, p.
239.
Toxic Materials News. 1979d. Federal Judge Allows Agent Orange Suit
Against Manufacturers. 6(48):381, November 28.
Toxic Materials News. 1979e. Toxic Materials News In Brief. November 28,
p. 383.
U.S. Code of Federal Regulations Title 21. 1978. Subpart D, Section
250.250. Hexachlorophene, as a component of drug and cosmetic products.
Effective January 19, 1978.
U.S. Dept. HEW. 1975. Center for Disease Control, NIOSH. Health Hazard
Evaluation Determination Report No. 74-117-251, December.
U.S. Dept. HEW. 1978. Bioassay of Hexachlorophene for Possible Carcino-
genicity. National Cancer Institute. Carcinogenesis Technical Report. CAS
No. 70-30 NCI-CG-TR-40, Series No. 40, p. 1.
232
-------
U.S. Environmental Protection Agency. 1975a. Destructing Chemical Wastes
in Commercial Scale Incinerators. Volume I, Technical Summary. July. NTIS
PB-257 709.
U.S. Environmental Protection Agency. 1975b. Hazardous Waste Disposal
Damage Reports. Document No. 2. EPA/530/SW- 151.2.
U.S. Environmental Protection Agency. 1977a. Destroying Chemical Wastes in
Commercial Scale Incinerators, Facility Number 1—The Marquat Company.
NTIS PB-265 451.
U.S. Environmental Protection Agency. 1977b. NAS. Drinking Water and
Health, PB-269519.
U.S. Environmental Protection Agency. 1978a. Ambient Water Quality Cri-
teria 2,3,7,8-TCDD. Washington, D.C.
U.S. Environmental Protection Agency. 1978b. Computer Data Files on Prior-
ity Pollutants in the Leather Tanning Industry, Lines 2261-8615. Research
Triangle Park, North Carolina.
U.S. Environmental Protection Agency. 1978c. Draft Report of the Ad Hoc
Study Group on Pentachlorophenol Contaminants. Environmental Health
Advisory Committee, Science Advisory Board. Research Triangle Park, North
Carolina.
U.S. Environmental Protection Agency. 1978d. Draft Status Report. Dioxin
in Industrial Sludges. Office of Solid Waste, Research Triangle Park, North
Carolina.
U.S. Environmental Protection Agency. 1978e. Notice of Rebuttable Pre-
sumption Against Registration and Continued Registration of Pesticide
Products Containing Pentachlorophenol. Federal Register, 43(202):
48443-48617.
U.S. Environmental Protection Agency. 1978f. Pesticide Product Information
on Microfiche, Chemical Reference File (Alpha). Research Triangle Park,
North Carolina.
U.S. Environmental Protection Agency. 1978g. Phase I Report on Hexachloro-
benzene (HCB). Research Triangle Park, North Carolina.
U.S. Environmental Protection Agency. 1978h. Rebuttable Presumption
Against Registration and Continued Registration of Pesticide Products
Containing 2,4,5-T. Federal Register, 43(78):17116-17157.
U.S. Environmental Protection Agency. 1978i. Rebuttable Presumption
Against Registration and Continued Registration of Pesticide Products Con-
taining 2,4,5-Trichlorophenol and Its Salts. Federal Register, 43(149):
34026-34054.
U.S. Environmental Protection Agency. 1979, The Presence of Priority
Pollutants in the Synthetic Manufacture of Pharmaceuticals. Draft.
233
-------
U.S. International Trade Commission. 1974, 1976, 1977. Synthetic Organic
Chemicals, United States Production and Sales.
U.S. National Institute of Environmental Health Sciences/International
Agency for Research on Cancer. 1978. Long-Term Hazards of Polychlorinated
Dibenzodioxins and Polychlorinated Dibenzofurans. Joint Working Group
Report, IARC, Lyon, France.
U.S. Patent Office. 1935. Patent No. 1,991,329. AlkaliMetal Trichloro-
phenolates.
U.S. Patent Office. 1939. Patent No. 2,176,417. Preparation of Penta-
chlorophenol.
U.S. Patent Office. 1941. Patent No. 2,250,480. Dihydroxy Hexachloro
Diphenyl Methane and Methods of Producing the Same.
U.S. Patent Office. 1943. Patent No. 2,319,960. Process for Producing
Halogenated Cresols.
U.S. Patent Office. 1948. Patent No. 2,435,593. Process for Making
Bis-(3,5,6-Trichloro-2-hydroxyphenyl) Methane.
U.S. Patent Office. 1949. Patent No. 2,471,575. Process of Preparing
2,4-Dichlorophenoxyacetic Acid.
U.S. Patent Office. 1950. Patent No. 2,509,245. 1950. Preparation of
2,4,5-Trichlorophenol.
U.S. Patent Office. 1952. Patent No. 2,599,516. 0-2,4,5-Trichlorophenyl
0,0-Dialkyl-thiophosphates.
U.S. Patent Office. 1955a. Patent No. 2,703,322. Poly Halo-salicylan-
iTides.
U.S. Patent Office. 1955b. Patent No. 2,728,799. Refinement of Benzene
Hexachloride.
U.S. Patent Office. 1956a. Patent No. 2,749,360. Esters of
a-2,4,5-Trichlorophenoxy-propionic Acid.
U.S. Patent Office. 1956b. Patent No. 2,754,324. cra-Dichloropropionates
of the Haloaryloxy Loweralkanols.
U.S. Patent Office. 1956c. Patent No. 2,756,260. Method of Making Tri-
chlorophenol Mixtures Which Are Rich in the 2,4,5-isomer.
U.S. Patent Office. 1956d. Patent No. 2,765,224. Herbicide.
U.S. Patent Office. 1957a. Patent No. 2,792,434. Process for the Produc-
tion of Hexachlorobenzene.
U.S. Patent Office. 1957b. Patent No. 2,799,713. Method of Making Tri-
chlorophenols From Tetrachlorobenzenes.
234
-------
U.S. Patent Office. 1957c. Patent No. 2,799,714. Method of Hydrolyzing
Di- and Trichlorobenzenes.
U.S. Patent Office. 1957d. Patent No. 2,812,365. Process of Preparing
Bis-(3,5,6-Trichloro-2-hydroxyphenyl) Methane.
U.S. Patent Office. 1957e. Patent No. 2,812,366. Improvements in the
Preparation of Polychlorophenols.
U.S. Patent Office. 1957f. Patent No. 2,812,367. Improvements in the
Preparation of Polychlorophenols in Aqueous Medium.
U.S. Patent Office. 1958a. Patent No. 2,830,083. Production of Aryloxy
Aliphatic Carboxylic Acids.
U.S. Patent Office. 1958b. Patent No. 2,849,494. 2,2-Thiobis (polyhalo-
phenols).
U.S. Patent Office. 1958c. Patent No. 2,852,548. Process for the Produc-
tion of Salts of Aryloxyalkanol-Sulfuric Acid Semiesters.
U.S. Patent Office. 1960a. Patent No. 2,922,811. Method for the Manu-
facture of 0-(Chlorophenyl)0,0-dialkylphosphorothiolates.
U.S. Patent Office. 1960b. Patent No. 2,947,790. Process for the Manu-
facture of 0-(Chlorophenyl)0,0-dialkylphosphorothiolates.
U.S. Patent Office. 1961a. Patent No. 2,980,681. Salt of Piperazine and
2,4,5-Trichlorophenol.
U.S. Patent Office. 1961b. Patent No. 3,005,720. Bacteriostatic Articles
and Method of Manufacture.
U.S. Patent Office. 1962. Patent No. 3,024,163. Bacteriostats.
U.S. Patent Office. 1963a. Patent No. 3,074,790. Method for the Control
of Undesired Vegetation.
U.S. Patent Office. 1963b. Patent No. 3,076,025. Process for Production
of Substituted Phenoxyalkanoic Acid.
U.S. Patent Office. 1967a. Patent No. 3,297,427. Synergistic Herbicidal
Composition and Method.
U.S. Patent Office. 1967b. Patent No. 3,347,937. 2,4,5-Trichlorophenol.
U.S. Patent Office. 1969. Patent No. 3,481,991. Preparation of Chlori-
nated Hydroxy Compounds.
U.S. Patent Office. 1971. Patent No. 3,607,949. Production of 2,2-
Methylenebis-(3,4,6-Trichlorophenol).
U.S. Patent Office. 1972. Patent No. 3,676,508. Process for the Manu-
facture of Carbon Tetrachloride.
235
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U.S. Patent Office. 1974a. Patent No. 3,816,268. Stabilized Distillation
of Pentachlorophenol.
U.S. Patent Office. 19745. Patent No. 3,852,160. Distillation of Penta-
chlorophenol with Sal icy!aldehyde and Water.
U.S. Patent Office. 1974c. Patent No. 3,852,161. Distillation of Penta-
chlorophenol .
U.S. Tariff Commission. 1968. Synthetic Organic Chemicals, United States
Production and Sales.
Van Miller, J. P., and J. R. Allen. 1977. Chronic Toxicity of 2,3,7,8-TCDD
in Rats. Fed. Am. Soc. Exp. Biol., 35:396.
Van Miller, J. P., J. J. Lalich, and J. R. Allen. 1977. Increased Inci-
dence of Neoplasms in Rats Exposed to Low Levels of 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin. Chemosphere, 6:537-544.
Van Miller, J. P., R. J. Marlar, and J. R. Allen. 1976. Tissue Distribu-
tion and Excretion of Tritiated Tetrachlorodibenzo-p-dioxin in Non-human
Primates and Rats. Fd. Cosmet. Toxicol., 14:31-34.
Verrett, J. 1970. Statement of Dr. J. Verrett, Food and Drug Administra-
tion, Department of HEW. In: Hearings Before the Subcommittee on Energy,
Natural Resources and the Environment of the Committee on Commerce, U.S.
Senate, Second Session on Effects of 2,4,5-T on Man and the Environment.
Serial 96-60, pp. 190-203.
Villanueva, E. C. , V. W. Burse, and R. W. Jennings. 1973. Chlorodibenzo-p-
dioxins Contamination of Two Commercially Available Pentachlorophenols. J.
Agric. Food Chem., 21(4):739-740.
Villanueva, E. C. , et al. 1974. Evidence of Chlorodibenzo-p-dioxin and
Chlorodibenzofuran in Hexachlorobenzene. J. Agric. Food Chem.,
22(5):916-17.
Vinopal, J. H. , and J. E. Casida. 1973. Metabolic Stability of 2,3,7,8-
Tetrachlorodibenzo-p-dioxin in Mammalian Liver Microsomal Systems and in
Living Mice. Arch. Environ. Contam. Toxicol., 1:122-132.
Vinopal, J. H., I. Yamamoto, and J. E. Casida. 1973. Preparation of
Tritium Labeled Dibenzo-p-dioxin and 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
In: Chlorodioxins—Origin and Fate, E. H. Blair, ed. Advances in
Chemistry, Series 120, American Chemical Society, Washington, D.C.
Viviani, A., et al. 1978. Time Course of the Induction of Aryl Hydrocarbon
Hydroxylase in Rat Liver Nuclei and Microsomes by Phenobarbital, 3-Methyl
Cholanthrene, TCDD, Dieldrin and Other Inducers. Biochemical Pharmacology,
27:2103-2108.
236
-------
Vos, J. G. , and L. Kater. 1978. Immune Suppression by TCDD. In: Dioxin--
Toxicological and Chemical Aspects, F. Cattabeni, A. Cavallaro, and G.
Galli, eds. SP Medical and Scientific Books, New York, London.
Vos, J. G. , and J. A. Moore. 1974. Suppression of Cellular Immunity in
Rats and Mice by Maternal Treatment With 2,3,7,8-TCDD. Int. Arch. Allergy
Appl. Immunol., 47:777-779.
Vos, J. G., J. A. Moore, and J. G. Zinkl. 1973. Effects of 2,3,7,8-Tetra-
chlorodibenzo-p-dioxin on the Immune System of Laboratory Animals. Environ-
mental Health Perspectives, 5:149-162.
Vos, J. G. , J. A. Moore, and J. G. Zinkle. 1974. Toxicity of 2,3,7,8-TCDD
in C57B1/6 Mice. Toxicol. Appl. Pharmacol., 29:229-241.
Vos, J. G., et al. 1978. Studies on 2,3,7,8-TCDD-Induced Immune Suppres-
sion and Decreased Resistance to Infection: Endotoxin Hypersensitivity,
Serum Zinc Concentrations and Effects of Thymosin Treatment. Toxicology,
9:75-86.
Wade, N. 1971. Hexachlorophene: FDA Temporizes on Brain Damaging
Chemical. Science, 174:805-807.
Walker, A. E., and J. V. Martin. 1979. Lipid Profiles in Dioxin-Exposed
Workers. Lancet, 446-7, February 29.
Wall Street Journal. 1979. EPA Orders Immediate Halt to Most Uses of
Herbicide 2,4,5-T and Similar Products. March 2.
Walsh, J. 1977. Seveso-The Questions Persist Where Dioxin Created a Waste-
land. Science, 197:1064-1067.
Ward, C., and F. Matsumura. 1977. Fate of 2,4,5-T Contaminant, 2,3,7,8-
Tetrachlorodibenzo-p-dioxin (TCDD) in Aquatic Environments. Department of
Entomology, University of Wisconsin. Technical Completion Report, Project
Number OWRT-A-058-Wis.
Ward, C. T. , and F. Matsumara. 1978. Fate of 2,3,7,8-TCDD in a Model
Aquatic Environment. Arch. Environ. Contam. Toxicol; 7(3):349-57.
Warnick, H. 1977. Memorandum to U.S. Environmental Protection Agency File.
Representative 2,4,5-T Labels. Research Triangle Park, North Carolina.
Warnick, H. 1978a. EPA Office of Pesticide Programs, personal communica-
tion, August 21.
Warnick, H. 1978b. EPA Office of Pesticide Programs, personal communica-
tions, October 20.
Wassom, J. S., H. E. Huff, and N. Loprieno. 1978. A Review of the Genetic
Toxicology of Chlorinated Dibenzo-p-dioxins. Draft Report. National Inst.
of Environ. Health Sciences, Inter-agency Agreement 40-247-70.
237
-------
Watkins, D. A. 1974. Implications of the Photochemical Decomposition of
Pesticides. Chemistry and Industry (London), 5:185-190.
Watkins, D. R. 1978b. Program for Prevention of Dioxin Exposure. U.S.
EPA, lERL-Cincinnati, Ohio. Unpublished.
Watkins, D. R. 1979a. History of Industrial Sample Containing Dioxin
(TCDDs). U.S. EPA, lERL-Cincinnati memo. March 27.
Watkins, D. R. 1979b. Personal communication. U.S. EPA, Environmental
Research Laboratory, Cincinnati, Ohio.
Watkins, D. R. 1980. U.S. EPA, lERL-Cincinnati, Ohio, personal communica-
tion.
Weissberg, J. B., and J. G. Zinkl. 1973. Effects of 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin Upon Hemostasis and Hematologic Function in the Rat.
Environmental Health Perspectives, 5:119-123.
Wertheim, E. 1939. Textbook of Organic Chemistry. The Blakiston Co. ,
Philadelphia.
Weitzman, L. n.d. Michigan Technological University grant proposal
entitled "The Utility of Wet Oxidation in the Treatment of Hazardous Organic
Wastes." Memorandum to Dr. E. Berkau, U.S. EPA, lERL-Cincinnati.
Westing, A. H. 1979. The Safety of 2,4,5-T. Science, 206:1135, December.
WGBH Educational Foundation. 1979. A Plague On Our Children. Nova
Transcript.
Whitemore, F. C. 1975. A Study of Pesticide Disposal in a Sewage Sludge
Incinerator. EPA/530/SW116c, NTIS PB-253 485.
Whiteside, T. 1977. A Reporter at Large: The Pendulum and the Toxic
Cloud. The New Yorker, July 25, pp. 30-55.
Wilkinson, R. R., G. L. Kelso, and F. C. Hopkins. 1978. State-of-the-Art
Report: Pesticide Disposal Research. EPA-600/ 2-78-183.
Wilkinson, R. D., et al. 1978. State-of-the-Art Report on Pesticide Dis-
posal Research. In: Disposal and Decontamination of Pesticides, M. V.
Kennedy, ed. ASC Symposium Series 73, American Chemical Society,
Washington, D.C., pp. 73-80.
Wilson, J. 1978. Breast Enlargement at an Italian School. Lancet,
1(8066):722.
Wipf, H. K. , et al. 1978. Field Trials of Photodegradation of TCDD on
Vegetation After Spraying with Vegetable Oil. In: Dioxin—Toxicological
and Chemical Aspects, F. Cattabeni, A. Cavallero, and G. Galli, eds. SP
Medical and Scientific Books, New York, London, pp. 201-216.
238
-------
Wong, A. S. , and D. G. Crosby. 1978. Decontamination of 2,3,7,8-Tetra-
chlorodibenzo-p-dioxin (TCDD) by Photochemical Action. In: Dioxin--Toxico-
logical and Chemical Aspects, F. Cattabeni, A. Cavallero, and G. Galli, eds.
SP Medical and Scientific Books, New York, London.
Woods, J. S. 1973. Studies of the Effects of 2,3,7,8-Tetrachlorodibenzo-p-
dioxin of Mammalian Hepatic S-aminolevulinic Acid Synthetase. Environmental
Health Perspectives, 5:221-225.
Woolson, E. A., and P. D. Ensore. 1973. Dioxin Residues in Lakeland Sand
and Bald Eagle Samples. In: Chlorodioxins: Origin and Fate, E. Blair, ed.
American Chemical Society, Washington, D.C., pp. 112-118.
Woolson, E. A., R.
rodi benzo-p-di oxi n
20(2):351-354.
F. Thomas,
Content in
and P. D.
Selected
Ensore. 1972.
Pesticides. J.
Survey of Polychlo-
Argic. Food Chem.,
World Health Organization. 1977. International Agency for
Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk
to Man. Some Fumigants, the Herbicides 2,4-D and 2,4,5-T,
Dibenzodioxins and Miscellaneous Industrial Chemicals. . Vol.
France, August.
Research on
of Chemicals
Chlorinated
15, Lyon,
World Health Organization. 1978. International Agency
Cancer. Information Bulletin on the Survey of Chemicals
Carcinogenicity. No. 7, Lyon, France.
for Research on
Being Tested for
Wright State University. 1979a. Report on Analyses of Love Canal Samples
for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). New York State Department
of Health Purchase Order No. 5975. January 21.
Wright State University. 1979b. Report on Analyses of Love Canal Samples
for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). For New York State Depart-
ment of Health. April 20.
Yang, K. H. , and R. E. Peterson. 1979. Differential Effects of Halogenated
Aromatic Hydrocarbons on Pancreatic Excretory Function in Rats. University
of Wisconsin, Madison.
Yang, G. C. , and A. E. Pohland. 1973. Cation Radicals of
Dibenzo-p-dioxins. In: Chlorodioxins--0rigin and Fate, E.
American Chemical Society, Washington, D.C. , pp. 33-43.
Chlorinated
Blair, ed.
Yates, P. B. 1979. Written communication to D. Watkins, U.S. EPA, IERL-
Cincinnati, from New South Wales State Pollution Control Commission,
Australia, January 18.
Yockim, R. S. , A. R. Isensee, and G. T. Jones.
Toxicity of TCDD and 2,4,5-T in an Aquatic Model
7(3):215-220.
1978. Distribution and
Ecosystem. Chemosphere,
239
-------
Young, A. L. 1974. Ecological Studies on a Herbicide-Equipment Test Area.
(TA C-52A) Eg!in AFB Reservation, Florida. Air Force Armament Lab, Tech-
nical Report AFATL-TR-74-12.
Young, A. L. 1978.
from USAF, August 23.
Written communication to D. Watkins, U.S. EPA, IERL,
Young, A. L., E.
Soil Persistence
the Weed Science
February 13.
Arnold, and A. M. Wachinsk. 1974. Field Studies on the
and Movement of 2,4-D, 2,4,5-T and TCDD. Presentation to
Society of America, Las Vegas, Nevada, Abstract No. 226,
Young, A. L. , C. E. Thalken, and W. E. Ward. 1975. Studies of the Ecolog-
ical Impact of Repetitive Aerial Applications of Herbicides on the Ecosystem
of Test Area C-52A, Eglin AFB, Florida. A.F. Armament Lab. AFATL-TR-75-142.
Young, A. L. ,
(TCDD) in the
USAFA-TR-76-18.
et al. 1976.
Environment:
Young, A. L. , et al. 1978.
Risk of Herbicide Orange and
Report TR-78-92.
Fate of 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Summary and Decontamination Recommendations.
The Toxicology, Environmental Fate, and Human
its Associated Dioxin. USAF, OEHL Technical
Zedda, S. , A. M. Cirla, and C. Sala.
TCDD, The ICMESA Incident. Medicina Del
1976. Accideatal Contamination by
Lavoro, 67(5):371-378.
Zinkl, J. G. , et al. 1973. Hematologic and Clinical Chemistry Effects of
2,3,7,8-Tetrachlorodibenzo-p-dioxin in Laboratory Animals. Environmental
Health Perspectives, 5:111-118.
Zitko, V., 0. Hutzinger, and P. M. Choi. 1972. Contamination of the Bay of
Fundy-Gulf of Maine Area With Polychlorinated Biphenyls, Polychlorinated
Terphenyls, Polychlorinated Dibenzodioxins, and Dibenzofurans. Environ-
mental Health Perspectives, 1:47.
240
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INDEX
Accumulation in plants, 129, 130
Acute toxicity, 169-173, 190-191
Aminophenols, 70
Aquatic toxicity, 169, 173
Bioaccumulation, 119-129
Bioconcentration, see bioaccumulation
Biodegradation, 98-102
Biomagnification, see bioaccumulation
Biological methods of disposal:
.Soil conditioning, 144
Wastewater treatment systems, 144, 145
Micropit disposal, 145, 146
Biological transport in animals, 118-129
Bithionol, 53, 54
Brominated phenols, 66, 67
Carcinogenicity, 182-184, 198
Chemical methods of disposal:
Ozone treatment, 140, 141
Chloroiodide degradation, 140, 142
Wet air oxidation, 142
Chlorinolysis and chlorolysis, 142, 143
Catalytic dechlorination, 143
Chlorophenols, 14-63
Manufacture, 17-24
Production, 24-26, 60, 61-63
Wastes, 58-59, 97, 131-133
Chronic toxicity, 173-180, 191-194
Combustion residues, dioxins in, 70-74, 89, 118, 132-133
241
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Comparative lethal doses, 169-171
Contaminated industrial wastes, 80-83
Cytotoxicity, 188, 189
2,4-D, 33-38, 41, 85, 86, 108, 122, 126, 134, 139
2,4-DB, 33-38
2,4-DEP, 33, 34, 36
DMPA, 39
2,4-DP, 33
Dermatologic effects, 174, 175
Dicamba, 56, 57
Dioxins produced for research purposes, 75, 76
Disposal or destruction of dioxins
Biological treatment, 58, 143-145
Catalytic dechlorination, 143
Chlorinolysis and chlorolysis, 142
Chloroiodide degradation, 140, 142
Concentration, 136, 138
Incineration, 132-134
Landfill ing, 59, 131-132
Microwave plasma, 136, 137
Molten salt combustion, 134-136
Ozonolysis, 140, 141
Photolysis, 138-139
Radiolysis, 139-140
Storage, 131
Wet air oxidation, 142
Dowlap, 57, 58
Embrotoxicity, 180-182, 194-197
Endocrine effects, 176
Enzyme effects, 154-157
Epidemiology, 190-199
Erbon, 46-48
Exposure, 77-97, 190-199
From foods, 86-88
From herbicide applications, 84-86
242
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From industrial accidents, 77-80, 191-194
From transportation accidents, 84
From waste handling, 80-83, 97
From water supplies, 87
In chemical laboratories, 96, 97, 191
In other related industries, 94-96
Occupational, 90-97
Fetotoxicity, 180-182, 194-197
Foods, dioxins in, 86-88
Gastrointestinal effects, 179
Gross and histopathologies, 159-169
Hematologic effects, 179
Hepatic effects, 175
Herbicide applications, 84-86
Herbicide Orange, 33, 36, 41, 82, 85, 96, 99, 100, 108, lil-114, 119, 120,
122, 133, 194, 198
Hexachlorobenzene, 59, 64-66
Hexachlorophene, 50-53, 77, 89, 97
Hexachlorophene exposures, 89, 90
Immunologic effects, 176-179
Incineration disposal methods, 132-137
Industrial accidents, 77-80, 90-94
Irgasan B5200, 57
Irgasan DP300, 57
Isopredioxin, 8
Lipids, effects on, 157-159
Metabolism, 149-159
Miscellaneous pesticide uses, 89
Mutagenicity, 188, 189
Neuropsychiatric effects, 179, 180
0-Nitrophenol, 67, 68
Particulate air emissions, dioxins in, 70-74
Pathophysiology, 189, 190
243
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Pentachlorophenol, 11, 12, 16, 17, 24, 25, 94-96
Pharmacokinetics and tissue distribution, 151-154
Photodegradation, 103-110
Physical methods of disposal, 136-140
Concentration, 136, 138
Photolysis, 138, 139
Radiolysis, 139, 140
Physical transport in air, 118
Physical transport in soil, 110-115
Physical transport in water, 115-118
Plastic, dioxins in, 74
Precursors, 3, 6, 8, 11, 12, 19
Predioxin, 8, 10-12, 57, 64
Renal effects, 175
Ronnel, 48, 49
Salicylic acid, 68-70
Sesin, 54, 55
Sesone, 36-39
Seveso, 77-80
Si 1 vex, 43, 45, 46, 84-86, 115, 126
Smiles rearrangement, 11
Soils, persistence in, 98-102, 110-115
2,4,5-T, 40, 41-44, 51, 81, 82, 84-87, 108, 111, 115, 117, 122, 123, 126,
127, 139, 195
2,4,5-Trichlorophenol, 27-33
Uses, 27
Manufacture, 28-31
Production, 31-33
Teratogenicity, 180, 181, 194-197
Transportation accidents, 84
Triclofenol piperazine, 55, 56
Tyrene, 58
Water supplies, dioxins in, 87
244
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
i. REPORT NO.
EPA-600/2-80-156
2.
3. RECIPIENT'S ACCESSI Of* NO.
4. TITLE AND SUBTITLE
Dioxins: Volume I
Sources, Exposure, Transport
and Control
5. REPORT DATE
June 1980
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
M. P. Esposito, H. M. Drake, J. A. Smith, and
T. W. Owens
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
PEDCo Environmental, Inc.
11499 Chester Road
Cincinnati, Ohio 45246
10. PROGRAM ELEMENT NO.
1BB610
11. CONTRACT/GRANT NO.
Contract No. 68-03-2577
12. SPONSORING AGENCY NAME AND ADDRESS
Industrial Environmental Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, Ohio 45268 '
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
EPA/600/12
15. SUPPLEMENTARY NOTES
Volume I of a three-volume series on dioxins
16. 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 volume reviews the extensive body of dioxin literature that has recently
Decome available. 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. This is followed by a detailed examination of the industrial sources of dioxins
hemical manufacturing processes which are likely to give rise to 2,3,7,8-TCDD and
other dioxin contaminants are thoroughly discussed. Other sources are also addressed
including incineration processes. Incidents of human exposure to dioxins are reviewed
and summarized. Reports on possible routes of degradation and transport of dioxins in
air, water, and soil environments are characterized. Current methods of disposal of
dioxin-containing materials are described, and possible advanced techniques for ulti-
mate disposal are outlined. Finally, an extensive review of the known health effects
of 2,3,7,8-TCDD and other dioxins is presented. This review emphasizes the results of
'ecent toxicological studies which examine the effects produced by chronic exposures
and also the various possible mechanisms of action for these toxicants.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
Organic chemicals
Pesticides; Herbicides
Biodeterioration
Toxicology
Waste disposal
Dioxins 2,3,7,8-TCDD
Environmental biology
Chemistry
Health effects
Hazardous wastes
07C
06F
11M
06T
13B
3. DISTRIBUTION STATEMENT
RELEASE TO PUBLIC
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
259
20. SECURITY CLASS (Thispage)
Unclassified
22. PRICE
EPA Form 2220-1 (9-73)
245
US GOVERNMENT HUNTING OfFICE 1980-657-146/5719
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