ENVIRONMENTAL CHEMICALS
HUMAN AND ANIMAL HEALTH
August 7-11, 1972
Fort Collins, Colorado
Sponsored by
Institute of
Rural Environmental Health
COLORADO STATE UNIVERSITY
And
U.S. ;ON AGENCY
Offi EPA 540/9-72-015 ls
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CONTENTS
Page
Contents ..... i
Preface . iii
Conference Participants v
Environmental Geochemistry in Missouri
Jon J. Connor, G. L. Feder, J. A. Erdman, R. R. Tidball. . 1
Trace Elements in Water
Albert V. Soukup 11
Mercury as an Environmental Pollutant
Michael G. Petit . . . 23
Molybdenum as an Environmental Pollutant
Gerald M. Ward . . 29
Lead in Soils and Plants
Robert L. Zimdahl, J. H. Arvik 33
Heavy Metal Poisonings in Animals
Arthur A. Case 41
Adverse Health Effects of Trace Materials in the Environment
Gory J. Love 45
Environmental Chemicals and Carcinogenesis
Hans L. Falk . . . 5?
Chemical Interactions
Frederick W. Oehme 65
Exposure Measurement
Anne R. Yobs 81
Polychlorinated Biphenyls (PCB's) in Humans
Anne R. Yobs 85
Epidemiology of Poisoning by Chemicals
Frank S. Lisella 93
Monitoring of Environmental Toxicants
John S. Wiseman 1Q7
The Analytical Laboratory (Panel Discussion)
Frederick W. Oehme, William D. Rhoads, Herbert Starr,
John Tessari 10,9
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CONTENTS (Continued)
Page
Polychlprinated Biphenyls in Silage and Human Milk in
Ryral Colorado
E. P. Savage, J. D. Tessari, J. W. Malberg, H. W. Wheeler,
J. R. Bagby, . ni
Interaction of PCB's and Other Organochlorines with Duck
Hepatitis Virus
Milton Friend, ........... . * . . 117
Carbon Monoxide as a National Problem
Richard E. Gallagher ..... ....,.,., 125
Carbon Monoxide Poisonings at High Altitudes
Freeman D. Fowler ................ 133
The Impact of Environmental Chemicals in Water in the .
Rocky Mountain Area
Charles G. Wilbur. ........ ...... 135
Nitrates and Water Quality
Janet G. Osteryoung ........... f 151
Air and Human Health
Gory J. Love ....................... 173
Teratogenesis and Mutagenesis of Environmental Chemicals
Hans L. Falk .......... '. , . . . ....... , 185
Pesticides in Air
Lawrence M, Mounce .,...,., . . , 193
USDA-APHS Environmental Statement
William M. Hoffman ......... . . 201
Polychlorinated Biphenyls: An Industrial Pollutant
Richard E. Johnsen 213
Epidemiology of Animal Poisonings Other Than Heavy Me£al
Poisonings
Frederick W. Oehme ........ .... 221
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Preface
These proceedings are made available to participants in the first
annual short course "Environmental Chemicals: Human and Animal Health,"
which was organized and presented by the Institute of Rural Environmental
Health, College of Veterinary Medicine and Biomedical Sciences, Colorado
v • ^
State University, Fort Collins, Colorado, in cooperatipn with the Office
of Pesticide Programs, Environmental Protection Agency.
The course was developed to update current knowledge about the rela-
tionships and interactions of chemicals in the environment and their
effects on human and animal health and to provide a forum for exploration
of these relationships by various disciplines. Topics represented a wide
range of thought, and we hope students will use the course proceedings to
further stimulate their own knowledge of and concern for influences of
chemicals on the environment.
Anne R. Yobs, M.D.
Course Chairman for:
Office of Pesticide Programs
Environmental Protection Agency
4770 Buford Highway
Chamblee, Ga. 30341
Eldon P. Savage, Ph.D.
Course Chairman for:
Institute of Rural Environmental Health
Colorado State University
Fort Collins, Colorado 80521
til
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CONFERENCE PARTICIPANTS
PROGRAM MEMBERS
John R. Bagby, Director, Institute of Rural Environmental Health,
Professor of Microbiology, Department of Microbiology, Colorado
State University, Fort Collins, Colorado
Bert L. Bohmont, State Chemical Coordinator, Department of Botany and
Plant Pathology, Colorado State University, Fort Collins, Colorado
A. A. Case, School of Veterinary Medicine, University of Missouri,
Columbia, Missouri
Gus Cholas, Institute of Rural Environmental Health, Associate Professor
of Microbiology, Department of Microbiology, Colorado State Univer-
sity, Fort Collins, Colorado
Jon J. Connor, Chief of the Branch of Regional Geochemistry, United
States Department of the Interior, Geological Survey, Denver, Colo-
rado i
Hans L. Falk, Associate Director for Programs, National Institute for
Environmental Health Sciences, Research Triangle Park, North Caro-
lina
Lloyd C. Faulkner, Professor and Chairman, Department of Physiology and
Biophysics, Colorado State University, Fort Collins, Colorado
Freeman D. Fowler, Private Physician, Box 36, Idaho Springs, Colorado
Milton Friend, Research Biologist, BSF&W, Denver Wildlife Research
Center, Federal Center, Denver, Colorado
Richard E. Gallagher, Bureau of Community Environmental Management,
Department of Health, Education, and Welfare, Public Health Service,
Parklawn Building, 5600 Fishers Lane, Rockville, Maryland
Dwayne W. Hamar, Department of Pathology, Colorado State University,
Fort Collins, Colorado
William M. Hoffman, Special Advisor to Deputy Assistant Administrator
for Pesticides Program, Environmental Protection Agency, Washington,
D.C.
Richard E. Johnsen, Associate Professor of Entomology, Colorado State
University, Fort Collins, Colorado
Lou Johnson, Physical Scientist, Air Quality Branch, U.S. Environmental
Protection Agency, Denver, Colorado
Roger Jordan, Assistant Professor, Department of Civil and Environmental
Engineering, University of Colorado, Boulder, Colorado
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Conference Participants (Cont.)
Frank Lisella, Assistant Director, Division of Pesticide Community
Studies, Environmental Protection Agency, Chamblee, Georgia
Gory Love, Assistant Director, Division of Health Effects Research,
National Environmental Research Center, Research Triangle Park,
North Carolina
Lauri Luoto, Associate Dean for Research, College of Veterinary Medicine
and Biomedical Sciences, Colorado State University, Fort Collins,
Colorado
Sumner M. Morrison, Director of Environmental Health Services, Professor
of Microbiology, Department of Microbiology, Colorado State Univer-^
sity, Fort Collins, Colorado
Lawrence Mounce, Director, Community Pesticides Program, Colorado
Department of Health, Greeley, Colorado
Frederick W. Oehme, Professor of Toxicology and Medicine, Director of
the Comparative Toxicology Laboratory, Department of Surgery and
Medicine, Kansas State University, Manhattan, Kansas
Janet G. Osteryoung, Institute of Rural Environmental Health, Assistant
Professor, Department of Microbiology, Colorado State University,
Fort Collins, Colorado
Michael G. Petit, Institute of Rural Environmental Health, Assistant
Professor, Department of Microbiology, Colorado State University,
Fort Collins, Colorado
Nicholas Pohlit, Executive Director of the National Environmental Health
Association, 1600 Pennsylvania, Denver, Colorado
William D. Rhoads, President and Director of Research, Analytical Devel-
opment Corporation, 1772 Lake Woodmoor Drive, Monument, Colorado
Eldon P. Savage, Chief, Chemical Epidemiology Section, Institute of
Rural Environmental Health, Associate Professor, Department of
Microbiology, Colorado State University, Fort Collins, Colorado
Albert V. Soukup, Chief, Water Supply Branch, U.S. Environmental Protec-
tion Agency, Denver, Colorado
Herbert Starr, Chemist, Community Pesticides Program, Colorado Department
of Health, Greeley, Colorado
Daniel T. Teitelbaum, Clinical Toxicologist, Internal Medicine, 2045
Franklin Street, Denver, Colorado
John D. Tessari, Chemist, Institute of Rural Environmental Health Labora-;
tory, Community Pesticides Program, Greeley, Colorado
William J. Tietz, Dean, College of Veterinary Medicine and Biomedical
Sciences, Colorado State University, Fort Collins, Colorado
VI
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Conference Participar.ts (Cont.)
Terry L. Thoem, Technical Advisor, Air Quality Branch, U.S. Environmental
Protection Agency, Denver, Colorado
Gerald M. Ward, Professor, Department of Animal Science, Colorado State
University, Fort Collins, Colorado
0. J. Wieman, Chief, Milk, Food and Drug Section, Colorado Department of
Health, 4210 East llth Avenue, Denver, Colorado
John Wiseman, Director, Community Pesticides Programs, Texas State Health
Department, Austin, Texas
Charles G. Wilber, Chairman and Professor, Department of Zoology, Colo-
rado State University, Fort Collins, Colorado
Gerald P. Wood, Director, Air Pollution Control Division, Colorado
Department of Health, 4210 East llth Avenue, Denver, Colorado
Anne R. Yobs, Chief, State Services Branch, Environmental Protection
Agency Division of Pesticides Community Studies, 4770 Buford High-
way, Chamblee, Georgia
Robert L. Zimdahl, Assistant Professor of Botany and Plant Pathology,
Colorado State University, Fort- Collins, Colorado
REGISTRANTS
Russell G. Arnold, Department of Health, Education, and Welfare, Rock-
ville, Maryland
C. Harold Baer, Bureau of Sport Fisheries and Wildlife, Denver, Colorado
Chester R. Ball, Food and Drug Administration, Denver, Colorado
Marvin P. Baumann, Central Michigan District Health Department, Gladwin,
Michigan
Ronald H. Bearden, Texas State Department of Health, Austin, Texas
Bernard L. Berger, Bureau of Sport Fisheries and Wildlife, Twin Cities,
Minnesota
James J. Boland, EPA, DPCS, SSM, Chamblee, Georgia
Virginia Boyes, Colorado Community Pesticide Study, Greeley, Colorado
J. Phillip Brewer, Colorado Community Pesticide Study, Greeley, Colorado
Andrew L. Bryson, Civilian Employees Health Clinic, Pueblo, Colorado
William C. Burnett, U.S. Food and Drug Administration, Kansas City,
Missouri
Gene A. Christiansen, North Dakota State Department of Health, Bismarck,
North Dakota
VII
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Conference Participants (Cont.)
I
W. Y. Cobb, North Carolina Department of Agriculture, Raleigh, North
Carolina
Troy Cole, Indian Health Service, Pheonix, Arizona
Susan Kay Dickinson, Colorado Community Pesticide Study, Greeley,
Colorado
Lawrence Durlin, Denver Department of Health and Hospitals, Denver,
Colorado
James 0. Ellis, Denver Wildlife Research Center, Denver, Colorado
John K. Emerson, Colorado Department of Health, Denver, Colorado
Truman Fergin, Denver Wildlife Research Center, Denver, Colorado ;
John I. Freeman, North Carolina State Board of Health, Raleigh, North
Carolina
Marvin H, Frye, Larimer County Health Department, Fort Collins, Colorado
William A. Gebhart, Engineer Command 101B2, Washington, D.C.
K. J. Goldsberry, Scott County Health Department, Davenport, Iowa
Bobby J. Gunter, DHEW - NIOSH, Region VIII, Denver, Colorado
M. A. Haegele, Denver Wildlife Research Center, Denver, Colorado
Lura E. Hager, Colorado Community Pesticide Study, Greeley, Colorado
Robert C. Hanisch, Colorado Community Pesticide Study, Greeley, Colorado
David C. Holland, Food and Drug Administration, Denver, Colorado
Don Holmer, Department of Community Health, Wichita, Kansas
Rick H. Hudson, Denver Wildlife Research Center, Denver, Colorado
David N. Ikle, Colorado Department of Health, Greeley, Colorado
Edward C. Knittle, Denver Wildlife Research Center, Denver, Colorado
Henry Koertge, University of Illinois - Health Service, Urbana, Illinois
Souheil Laham, Department of National Health and Welfare, Ottawa, Canada
Bob LaRue, Department of Agriculture, Helena, Montana
Morris R. Levy, DHEW, PHS, FDA, Baltimore, Maryland
L. G. Linn, State of Alabama, Health Department, Montgomery, Alabama
viii
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Conference Participants (Cont.)
S.M. Sgt. John L. Lund, USAF School of Aerospace Medicine, Brooks AFB,
San Antonio, Texas
Tim Lusk, Health Department, Hickman, Kentucky
Cpt. John Mogelnicki, Fort Carson Army Base, Colorado Springs, Colorado
E. Edsel Moore, Kentucky State Department of Health, Frankfort, Kentucky
Kurt W. Moore, Denver Wildlife Research Center, Aurora, Colorado
William E. Morton, University of Oregon, Portland, Oregon
William C. Mulcahy, Scott County Health Department, Benton, Missouri
Gene J. Nandrea, Food and Drug Administration, Denver, Colorado
Melvin T. Okawa, NIOSH - USPHS, San Francisco, California
Glenn Orr, Department of Community Health, Wichita, Kansas
Robert A. Poss, Environmental Protection Agency, Seattle, Washington
Jorge Pujol, Ministerio de Salud, Panama, Republic de Panama
Jack L. Radomski, University of Miami, Miami, Florida
Howard L. Richardson, Pesticides Office Programs, Washington, D.C.
H. Gerritt Rosenthal, Lane County Health Department, Eugene, Oregon
Katherine P. Schirmer, Environmental Protection Agency, Washington, D.C.
Henry C. Schroeder, Environmental Protection Agency, Portland, Oregon
Franklin M. Sharit, Navy Disease Vector Ecology and Control Center,
Alameda, California
Phillip Shoultz, U.S. Public Health Service, Window Rock, Arizona
Arnold Slonim, Aerospace Research Laboratory, Dayton, Ohio
Ann L. Smrek, Clinical Toxicology Laboratory, Atlanta, Georgia
John E. Towle, Tri-County District Health Department, Aurora, Colorado
Frank Triska, Pueblo Army Depot, Pueblo, Colorado
Gary Tye, Analytical Development Corporation, Monument, Colorado
Kit Walther, Environmental Services Bureau, Helena, Montana
Maurice Weeks, U.S.A. Environmental Hygiene Agency, Edgewood Arsenal,
Maryland
IX
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Conference Participants (Cont.)
Lt. William Weiss, U.S. Public Health Service, Window Rock, Arizona
Dale Wells, Environmental Protection Agency, Denver, Colorado
Donald Whitcomb, Arizona State Health Laboratory, Phoenix, Arizona
E. A. Widmer, Loma Linda University, Loma Linda, California
Daniel P. Wojcik, USDA, ARS, ENT, Gainesville, Florida
Donald W. Woodham, Environmental Quality Lab, USDA, Brownsville, Texas
Mitchell J. Wrich, Environmental Protection Agency, Region V, Chicago,
Illinois
Jeff Wagenet, Graduate Student, Oklahoma City, Oklahoma
COLORADO STATE UNIVERSITY FACULTY REGISTRANTS
Fred M. Applehans
William Brown
Laurier P. Couture
Gred Freden
Joseph W. Malberg
Fred L. Vogt
H. William Wheeler
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ENVIRONMENTAL GEOCHEMISTRY IN MISSOURI--
A MULTIDISCIPLINARY STUDY*
J. J. Connor, G. L. Feder, J. A. Erdman, and R. R. Tidball
Abstract
Current interest in the geochemistry of the natural environment as it
may affect human and animal health prompted the U.S. Geological Survey
to begin a wide-ranging program of geochemical studies in the State of
Missouri. Out of this program has emerged a general 4-stage sampling
plan suitable for geochemical surveys of large regions; the number and
choice of stages executed in any one survey depend on the detail of
information required. The great diversity of natural materials in
Missouri includes at least eight broad geohydrologic units, some 150
named rock units, more than 275 named soil series, and six vegetation-
type areas encompassing 2400 native plant species; and it poses a
difficult challenge in sampling design. Work to date has centered on
the search for and definition of a minimum number of geochemically co
coherent categories of environmental materials whose members will
exhibit as much geochemical uniformity as possible in comparison with
differences among categories. Preliminary data indicate that (1) the
geohydrologic units are geochemically distinct, (2) the rocks consist
of perhaps as few as six important broad-scale geochemical types, (3)
the soils are chemically indistinct when classified by conventional
criteria and are better characterized by landscape type, and (4) vege-
tation-type areas as measured by selected plant species and associated
soils appear to be distinct in trace-element composition.
Scope and Purpose of Study
The recent increased concern about the role of trace elements in health
and nutrition has spurred an interest in the distribution and availabil-
ity of nearly all elements in the environment. Probably the best known
hazardous elements in the environment are Pb and Hg, but medical research-
ers (3) suggest that Ag, Cd, Sn, Ti, Al, Bi, Au, Ga, Ge, and Zr may also
be "environmental contaminants" in living tissue. The same researchers
note that Cu, Zn, Mn, Co, Mo, Se, Cr, Fe, and I have been identified as
trace elements essential to biochemical function of some kind and that
Rb, B, Ba, Sr, F, V, Ni, As, and Br (as well as some of the previously
mentioned elements) appear to be ubiquitous in plants and animals.
The interest of medical workers in the trace-element environment prompted
the U.S. Geological Survey to start a geochemical survey of the natural
environment in the State of Missouri. The survey was begun in July 1969
in cooperation with the Environmental Health Center of the University of
Missouri. The major purpose of the survey is to provide useful back-
ground or baseline data on the general geochemical setting in the State,
which will allow an accurate assessment of local geochemical conditions.
*Reprinted from Geology and'the Quality of Life, Symposium 1, International
Geological Congress, 24th Session, Montreal, Canada, 1972.
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The survey consists of four parts directed at the chemistry of the
rocks, the waters, the soils, and the vegetation. The primary objec-
tive is to determine the regional variations in the chemical charac-
teristics of each of these materials. This information will be used
by epidemiologists of the Environmental Health Center in searches for
relationships between geochemistry and human or animal health. It
may also be useful in obtaining a better understanding of the mechanisms
operating in the transfer of trace elements between media.
The great diversity of natural materials in Missouri includes eight
broad geohydrologic units, about 150 named rock formations, more than
275 named soil series, and about 2400 native plant species that occur
in six major vegetation-type areas. This diversity is a difficult
challenge to effective environmental characterization and requires a
carefully planned sampling program in order to obtain maximum infor-
mation from minimum sampling and analytical costs.
Sample Design
The sampling designs in this program are based on broad categories
within each of the major natural sampling media—rocks, waters, soils
and plants. Each broad category is chosen such that its components
will exhibit as much geochemical uniformity as possible in comparison
with differences among categories. For example, rock categories are
defined on a lithdlogic basis because geochemical variation within a
lithologic type is expected to be small in comparison to the variation
between types. After the sampling categories are defined, the sampling
can proceed in as many as four stages:
Phase 1: Sampling to describe differences among categories.
Stage la: Preliminary sampling designed to determine the extent to
which the categories are indeed geochemically distinct, and
to provide the basis for planning Stage Ib.
Stage Ib: Final sampling to derive reliable estimates of differences
among categories, and the amounts of compositional vari-
ability within each category.
Phase 2: Sampling to describe patterns of variation within categories.
Stage 2a: Preliminary sampling within each category to determine the
sampling locality spacing that would be most efficient for
describing the geochemical variation patterns within each
category, and the number of samples required from each
locality.
Stage 2b: Final sampling to describe the geochemical patterns within
each category.
The basic statistical model for Stage la sampling is based on the
hierarchical case of the analysis of variance and is used to estimate
components of geochemical variation thought to be important. Compo-
nents commonly estimated are those reflecting (1) variation among
categories, (2) variation at large sample intervals within categories,
(3) variation at shorter sampling intervals, and (4) variation in
laboratory procedures (analytical reproducibility).
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This model is written:
Xljkl ' " + ai + B1J + ^ijk + 6ijkl
where X. .,.. is the value of some element reported by the analyst and y
is the average concentration for that element in the medium under study.
The remaining terms reflect the combined effects of the four components
of variation in that particular analytical value. They are assumed to
be random variables with means of zero and variances of a£, a2;, a.2, and
a2;, and are estimated by subdividing the total observed variance into
four parts:j
S2 „ S2 - S2 . S2 . 82 , (2)
8X sa + S6 + SY S6 . UJ
where sj^ is the observed variance in X, and the four terms on the right
are estimates of the four components of interest. Components may be
added to or deleted from (1) or their definition may be changed to meet
the peculiarities of a particular field problem. Because most trace-
element data in environmental geochemistry approximate a log-normal
frequency distribution, the variances are commonly derived from loga-
rithmically transformed data.
It may happen that the results of Stage la sampling adequately distin-
guish among categories and that Stage Ib sampling is not necessary. A
quantitative assessment of this contingency is possible by comparing
the among-category variance (s2,) to the variance of the category means
computed from the Stage la sampling results. The variance of the
category means is estimated from:
s2 s2 s2
sm= nnr+ rJ-+ £ (3)
where s£ is the variance of a category mean and n^, ny, and ng are the
numbers of sampling units at each of the three lower levels of the
design. The ratio:
V = s2/s2 (4)
mam
compares the magnitude of the category differences to the imprecision
in estimating those differences. Preliminary computer simulation
experiments suggest that the absolute minimum acceptable value of Vm
is about 1.0. Where Vm is less than 1.0, additional sampling (Stage Ib)
is required.
Environmental Categories
The rocks. The distribution of rock units in Missouri is shown in
Figure 1. Overlying the bedrock units in northern Missouri are exten-
sive deposits of glacial materials and in southern Missouri extensive
deposits of clay-rich residuum resulting from the weathering of carbon-
ate bedrock. The six most important categories of geologic materials in
Missouri, in an environmental sense, are (1) glacial deposits of Quater-
nary age, (2) carbonate residuum of Cenozoic age, (3) shale and (4)
limestone, both of Pennsylvanian age, (5) limestone of Mississippian
age, and (6) dolomite of Cambrian-Ordovician age.
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EXPLANATION
. Southern limit of
'••' glocidtion
Quaternary rocks
Tertiary-Cretaceous rocks
Pennsylvanian rocks
Mississippian rocks
Devonian-Silurian
Ordovician rocks
Ordovician rocks
Precambrian rocks
100, Km
Scale
North
Figure 1. Generalized geologic map of Missouri. Modified from
American Association of Petroleum Geologists (1966).
The carbonate residuum, Category 2, consists of a red, clay-rich,
cherty material representing the accumulated residue of subaerial
weathering of carbonate bedrock. In general, the shale contains more
trace elements in greater concentrations than rocks in the remaining
five categories; loess, which is related to the glacial deposits of
Category 2, tends to be high in the alkali and alkaline earth metals;
and the limestones and dolomites are the poorest in trace elements.
The geochemical disparity among these categories is obvious and the
among-category component of variance was not included in the statisti-
cal model used for rock sampling. Instead, separate models were defined
for each category. Each model included a stratigraphic component of
variance reflecting variation across the geologic section as well as
geographic and analytical components.
The waters. Seven geohydrologic categories of potable ground water
have been sampled in Missouri. An eighth category—ground water in
the Precambrian crystalline rocks—is of such limited use that it was
excluded from this study. The geohydrologic categories closely
parallel some of the major rock categories because of the important
physico-chemical control exercised by the rock reservoir on the
contained water.
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The geohydrologlc units are (1) water from the Quaternary alluvium,
(2) water from Quaternary glacial drift, (3) water from Cretaceous and
Tertiary strata, (4) water from Pennsylvanian strata, (5) water from
Mississippian strata, (6) water from Cambrian-Ordovician strata in
southwestern Missouri, and (7) water from Cambrian-Ordovician strata
in southern and southeastern Missouri.
In general, ground water from the glacial drift and from the Pennsyl-
vanian strata contains higher concentrations of trace elements than
ground water from the other units.
The statistical model used in the Stage la sampling of ground waters
contains four components, as given in Equation 1.
In addition to estimating the variance among the seven geohydrologic
units (categories), large-scale variation within units was estimated by
sampling water from five randomly selected townships within each unit;
small-scale variation was estimated by sampling two wells within two of
the five townships; and sample variation (including analytical repro-
ducibility) was estimated by sampling one well in each unit twice at
randomly selected intervals over a period of three months.
The soils. Category definition has proved to be less tractable among
Missouri soils than for the other media. There is a great diversity in
the soils as expressed in the taxonomic criteria of the standard soils
classification system (4). This system contains six taxonomic levels
and some 275 soil series (one of the lower taxonomic level) in Missouri.
A preliminary study based on the A-horizon (or surface layer) was used
to estimate the kind and magnitude of chemical variability associated
with three of these taxonomic levels (5). The results demonstrate that
the use of soil series as sampling categories would permit description
of some 60% of the total compositional variability in Missouri soils,
but such categorization would result in unacceptably large sampling and
analytical costs. Therefore, attention has focused on alternative
classification criteria.
Another study of the chemical variability of Missouri soils was based
on variation in the B-horizon of uncultivated soils in the six vegeta-
tion-type areas of the State (Figure 2). The data obtained indicate
that, for purposes of describing geochemical variations, classification
of the soils by vegetation-type area is more effective than classifica-
tion by the standard system. The vegetation-type areas in Missouri are
(1) Floodplain Forest (soils here are developed largely on alluvium
along the Mississippi River), (2) Glaciated Prairie (soils here are
developed mostly on glacial deposits), (3) Unglaciated Prairie (soils
here are developed mostly on shale and limestone), (4) Cedar Glade
Forest (soils here are developed mostly on carbonate residuum), and
(6) Oak-Hockory-Pine Forest (soils here are developed on granitic rocks,
sandstone, and carbonate residuum).
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EXPLANATION
u
c
Glaciated Prairie
Unglaciated Prairie
0 | Oak -Hickory Fprest
OP j Oak- Hickory-Pine Forest
Cedar Glade
Floodplain Forest
100 Km
Scale
North
Figure 2. Generalized vegetation-type areas in
Missouri. Modified from Kuchler (1964).
B-horizons of uncultivated soils from both prairie areas generally
appear to be the richest in trace elements of any in the State, whereas
B-horizons of uncultivated soils from the Oak-Hickory-Pine Forest are
the poorest in trace elements.
The statistical model for Stage la and Stage lb sampling in this study
also contained four components of variation. One component reflected
differences among soils from the six vegetation-type areas, a large-
scale component reflected differences among soils from different 7%
minute quadrangles within each area (5 quadrangles were sampled in each
vegetation-type area in Stage la; 10 in Stage lb), and a small-scale
component reflected differences among soils within quadrangles (2
samples were collected within quadrangles in Stage la; 5 in Stage lb).
A component of analytical reproducibility for these soil samples was
estimated from an independent study for Stage la but was estimated as
an integral part of the experiment in Stage lb.
Additional studies of chemical variability among Missouri soils are
directed at the importance of parent material in determining chemical
characteristics and at the chemistry of the surface horizons of agri-
cultural soils.
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The plants. About 2400 distinct native plant species have been recog-
nized in Missouri; because their complete chemical characterization is
impossible, the main effort in the plant study is directed at the
chemistry of two species that are widespread throughout the State.
The dominant species in each vegetation-type area are also being
studied (Figure 2).
The two selected widespread species are smooth sumac (Rhus glabra) and
buckbrush (Symphoricarpos orbiculatus) and are intended to serve as
indicator plants which may reflect geographic differences in plant
response to the gedchemical environment. Samples of smooth sumac were
taken at each site where the B-horizon of uncultivated soils was
sampled. The statistical model and sampling plan, therefore, are
identical to those for uncultivated soils previously described.
Samples of buckbrush were collected during Stage Ib sampling as an
alternative indicator; species.
Geochemical Variability in Missouri and its Implications
• •• • .,-. •"'•*.
Estimates of some of the variance components derived from Phase 1
sampling of ground water, uncultivated soil, and smooth sumac over the
entire State are shown in Table 1. Most elements in ground water
exhibit geographic variance components, like those of Sr and carbonate
hardness. That is, variation between wells within a township is small
compared with variation on larger scales (between townships). Commonly,
the variation among townships within geohydrologic units is as great
or greater than that among units. However, pH is the only chemical
property measured that yielded a ratio, Vm, much below unity. Most of
the ratios are considerably higher, and the results of Stage la sampling
are deemed sufficient for obtaining satisfactorily stable estimates of
the average differences among the waters from the seven broad geohy-
drolic units in the State. It also seems likely that environmental
responses to most aspects of ground-water chemistry, if present, should
vary as much or more within the major parts of the State underlain by
the geohydrologic units as they do among those parts. In ^general, they
should not vary greatly within small areas;
The double entries for uncultivated soils in Table 1 are completely
independent estimates of the variance components obtained from Stage la
and Stage Ib sampling. Most elements in the soils have variance
components similar to those of Sc and V. That is, variance between
quadrangles widely distributed over the vegetation-type areas is small
in comparison with that between areas and between sampling sites within
quadrangles. This property of the variance was exploited in the Stage
Ib sampling by increasing the sampling density within quadrangles and
sampling only 10 quadrangles. Thus, although five times as many
samples were collected in Stage Ib as in Stage la, it was necessary to
sample only twice as many quadrangles. As shown in.Table 1, the
results of the Stage Ib sampling yielded substantially higher Vm ratios,
and, hence, substantially more stable estimates of the chemical
differences among the soils of the six vegetation-type areas. As for
the possible epidemiological implications, any plant and animal res-
ponses to the chemistry of the''soils in Missouri can reasonably be
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TABLE 1
Components of logarithmic variance of selected geochemical properties in
ground water, uncultivated soil, and stems of smooth sumac in Missouri.
Ground Water
Variable
PH1
Li
Sr
Carbonate
hardness
Between
Samples.
(86>
0.0250
.0090
.0018
.0004 '».-.
Between
Wells
0.0125
.1793
.0150
.0081
Between
Between Geohydrologic
Townships Units
0.1516
.1939
.1402
.0954
0.0070
.3421
.1570
.0479,
. Uncultivated Soils (B-horizon)
(Upper entry estimated from results of Stage la
lower entry from Stage Ib sampling)
Variable
\
Ba
Cu
Sc
v
Between
Analyses
<8S>-
0.0056
.0131
.0114
.0349
.0023
" .0084 '
.0060
.0052
Between
Sites
(8Y}
0.0292
.0187,
.0171
.0285
.0208
.0168
.5275
.0264
Between
Quad-'
rangles
<83>
0.0063
'.0163
.0270
.0090
.0030
.0065
.0062
.0074
Smooth Sumac
Variable
Mn
B
Ba
Cu
Pb
Between
Analyses
t
No data
No data
No data
No data
No data
Between
Sites
0.0240
.0133
.0779
.0171
.0482
Between
Quad-
rangles
0.0270
; 0
.0289
.0061
.0013
Between
, Vegetation-
Type Areas
^8or
0.0177
.0212
.0085
.0091
.0314
.0206
.0345
.0287
(Stems)
Between
Vegetation--
Type Areas
0.0203
* 0 '
,1412 f
.0097
.0079
Variance
of Unit
Means
0.0378
.0764
.0314
.0208
sampling;
Variance
of Unit
Means
"
0.0047
.0023
.0083
.0022
.0029
.0012
.0113
.0014
Variance
of Unit
Means
0.0078
.0013
.0136
.0029
.0051
-------
expected to vary among the major vegetation-type areas. Also, little
variation in response should be expected on a broad scale within
vegetation-type areas—assuming, of course, that the response is a
direct and simple effect of some element, or combination of elements,
having the type of variability that has been found for most elements.
Where the response results from a combination of environmental factors,
of which soil chemistry is only one, its pattern of variation will be
less predictable.
Stems of smooth sumac, like the B-horizons of uncultivated soils, vary
comparatively little in composition over broad parts of the same
vegetation-type area, but do tend both to vary among areas and to vary
locally within areas (between sites). However, there appears to be
little correspondence between element concentrations in sumac stems
and element concentrations in the soil. Comparison of mean element
concentrations in the two media in each vegetation-type area indicates
that of those elements studied, only Fe in sumac apparently reflects
the elemental soil concentrations. Element concentrations in sumac,
therefore, may be related more to soil pH and soil moisture, which
affect availability, than to the total element concentrations in the
substrate.
In conclusion, the sampling approach being tested in the Missouri survey
appears to be practical for problems arising in geochemical surveys of
large regions. Phase 1 sampling has identified the gross geochemical
variations over the State and can provide epidemiologists with what may
be regarded as first-order geochemical maps—that is, maps showing the
chemical differences in the rocks, soils, plants, and water among the
major parts of the State. If more detailed information on the geochemi-
cal variability is needed, Phase 2 sampling may be done in order to
describe the geochemical variation patterns within parts of the State.
Whether or not more detailed information is needed will not be known
until the data from Phase 1 have been thoroughly examined by the epidemi-
ologists.
References Cited
1. American Association of Petroleum Geologists. 1966. Geological
highway map of the mid-continent region. Amer. Assoc. Petroleum
Geologists, U.S. Geol. Highway Map 1.
2. Kuchler, A. W. 1964. Potential natural vegetation of the conter-
minous United States. Amer. Geog. Soc. Spec. Pub. #36.
3. Selby, L. A., C. J. Marienfeld, and 0. J. Pierce. 1970. The effects
of trace elements on human and animal health. J.A.V.M.A. 157(11):
1800-1808.
4. Soil Survey Staff. 1970. Selected chapters from the unedited text
of the soil taxonomy of the National Cooperative Soil Survey. Soil
Conservation Service, U.S. Dept. Agr., Washington, D.C.
5. Tidball, R. R. 1971. Geochemical variation in Missouri soils. In
Trace Substances in Environmental Health - IV, p. 15-25. Ed. D. D.
Hemphill, Univ. Missouri, Columbia, Mo.
-------
TRACE ELEMENTS IN WATER
Albert V. Soukup
"Good afternoon, ladies and gentlemen, this is your local radio station,
K- - -, with its regular 'phone-in-and-talk program. Just call 123-4567
and you will be on the air." Buzz, buzz. "This is Joe Crackpot. I've
just put cyanide into the city water supply!"
Sound far fetched? No, not indeed I Essentially, this event occurred
within the last three months in a city in this part of our nation.
Luckily, it was only a false alarm.
How does this relate to trace elements in water? Perhaps we need to
know the significance of these elements and their effect on Homo sapiens
and/or animals. Our Congress is interested, as stated in a proposed
amendment, #410, to Senate Bill 1478, which states
....that increasing quantities and types of pesticides, organic
chemicals, toxic metals, and other contaminants are entering
the public water systems that serve as sources which supply
the nation with water for drinking, recreation, and other
human uses; that many of these new contaminants are either
not detected or not removed by established water testing
and treatment methods; and these contaminants are consumed
by the public or otherwise come into contact with the public
thereby presenting a potential hazard to the public health.
They have proposed in the bill that research be done on
(A) improved methods and procedures to identify and measure
the existence of pesticides, toxic metals, organic chemicals,
radioactive substances, bacteria, viruses, and other contam-
inants in water used for drinking, recreation, and other
human uses;
(B) improved methods and procedures to identify and measure
the health effects of pesticides, toxic metals, organic
chemicals, radioactive substances, bacteria, viruses, and
other contaminants in water used for drinking, recreation,
and other human uses."
Hundreds of new chemical compounds are being introduced into our environ-
ment annually. Few of these are assessed for their potential impact on
the health of man, particularly on the synergistic effect they may have
when acting together or in concert with other types of environmental
stresses. Some of these chemicals, although at higher concentrations
than are likely to be found in water, have been shown to cause cancer,
genetic damage, or malformations at birth.
The impact of the long-term ingestion of low levels of chemical contami-
nants is very difficult to ascertain. Because the effects of such
chemicals ingested in low concentrations over long periods are slow and
insidious, and are likely to be similar to those effects manifested by
aging or other chronic diseases, their significance is particularly
difficult to establish.
11
-------
However, we know that carcinogens, mutagens, and teratogens are being
discharged in waste waters and become part of the water supply of a
substantial portion of the population. For example, waste waters in
England have been shown to contain two well-established carcinogens,
2,4-benzpyrene and 1,2-benzanthracene, albeit at low concentrations.
Other hazards likely to be found in.polluted waters include petroleum
products and aromatic amino and nitro compounds. Radioisotopes, par-
ticularly in concert with other chemicals, constitute cancer hazards to
the general population.
The highly toxic pesticides are particularly troublesome, often not
because of the toxic effect of the chemical itself, but because of highly
toxic impurities that result from their manufacture.
Monitoring of these chemicals and tracing their fate in our water manage-
ment programs and treatment processes is absolutely essential if we are
to assure Americans of the safety of their public water supplies. We
must not learn of the health effects of these chemicals after they have
occurred, thereby using Americans as guinea pigs.
Now, to the esthetic quality of water. Rapidly growing population and
increasing rates of urbanization and industrialization are exerting
greater and greater pressures on our limited water resources.
Although nature renews the volume of fresh water available, we have been
profligate in its use so that communities have had increasingly to turn
to polluted sources to meet their needs. Where once we boasted of the
salubriousness and the quality of our water supplies, now we grudgingly
accept the product provided, often with distaste. We have all seen the
signs reading somewhat as follows: "Please flush the toilet, our neigh-
bors downstream need the water."
Waters drawn from highly contaminated sources require the addition of
many chemicals that may render the water distasteful, and many people
have turned to bottled waters. Ironically, bottled waters do not under-
go the surveillance that public supplies do and are often less safe, as
shown recently by the Washington Star.
Unless we make a commitment to improve public water supply systems, our
proud heritage of quality water will have been lost.
It is argued sometimes that trace elements of unknown relationship should
be tolerated in waters because no immediate relationship to man is ap-
parent. Conversely, we should not wait for the best criteria, as stated
by Dr. Abel Wolman. To paraphrase him, the best criterion for detecting
a dangerous public water supply is the doctor's certificate showing that
the man is dead and the epidemiologic evidence showing that the water he
drank killed him.
So then, how do we consider limits of trace elements? These considerations
must include the element or compound, its effect upon health and well-
being, the allowable limit, and the concentration in the water versus the
12
-------
Table 1
Health and aesthetic significance of trace elements and compounds and their occurrence in U.S.
water supplies.
or Compound
Alkyl benzine
1962
USPHS
Drinking
Water
Standards
Health or Aesthetic Effect mg/1
USPHS limit gives a safety factor of 15,000; 0.5*
Occurrence in U.S.
Water Supplies
2,595 Distribution
Samples (1969)
mg/1
Average Range
0.05 0-0.41
sulfonate (ABS)
Arsenic (As)
Chloride (Cl~)
Copper (Cu)
Carbon Chloroform
Extract (CCE)
Cyanide (CN~)
Fluoride (F~)
Nitrate (N03)
Sulfate (S04)
Zinc (Zn)
Barium (Ba)
Cadmium (Cd)
Chromium (Cr"1"6)
Lead (Pb)
Selenium (Se)
Silver (Ag)
Radium (Ra-226)
Strontium (SR-90)
not highly toxic.
Serious systemic poison—100 rag usually
causes severe poisoning, is cumulative,
and may cause chronic effects. Late
evidence indicates tiny amounts may be
beneficial.
Limit set for taste reasons.
Body needs copper at level of about a mg/day
for adults; not a health hazard except
when large amounts are ingested.
At limit stated, organics in water are
. not considered a health hazard.
Rapid fatal poison, but limit set provides
safety factor of about 100.
Beneficial in small amounts; above 2,250
mg dose can cause death.
Excessive amounts can cause methemo-
. globinemia (blue baby) in infants.
Above 750 mg/1 usually has laxative effects.
Zinc is beneficial in that a child needs
0.3 mg/kg/day; 675-2,280 mg/1 may be an
emetic.
?atal dose is 550-600 mg as the chloride;
muscle (including heart) stimulant.
13-15 ppm in food has caused illness.
Limit provides a safety factor. Carcino-
genic when inhaled.
Serious, cumulative body poison.
Toxic to both humans and animals in large
amounts. Late research suggests small
amounts may be beneficial.
Can produce irreversible, adverse cosmetic
changes.
A bone-seeking, internal alpha emitter
that can destroy bone marrow.
A bone-seeking, internal beta emitter.
0.01* 0.0001 <0.03-0.10
o.ost
250*
1*
27.6
0.13
1.0-1.950
0-8.35
0.2* 0.11 0.008-0.56
0.01* 0.00009 <0.1-0.008
0.2t
0.7-1.2* 0.32 <0.2-4.40
1.4-2.At
45*
250*
5*
l.Ot
O.Olt
O.OSt
0.05*
O.Olt
6.3
46
0.19
0.034
0.003
0.0023
0.013
0.003'
<0.1-127
<1.0-770
0-13.0
0-1.55
<0.2-3.94
0-0.079
0-0.64
0-0.07
O.OSt 0.008 0-0.03
3 pc/l+ 2.2 pc/1 0-135.9 pc/1
10 pc/lt <1.0 pc/1 0-2.0 pc/1
* Not to be exceeded where other more suitable supplies are, or can be made, available.
t Excess constitutes grounds for rejection of the supply.
J Consult 1962 "USPHS Drinking Water Standards" for interpretation.
13
-------
allowable limit. Table 1 indicates limits of the U.S. Public Health
Service Drinking Water Standards (1), and Table 2 indicates limits not
found in that manual but generally followed by the Water Supply Division
of the Environmental Protection Agency. These two tables are reproduced
through the courtesy of Floyd B. Taylor, Sanitary Engineer Director of
the U.S. Public Health Service, from a paper presented at a Pacific
Northwest Section meeting of the American Water Works Association on
May 13, 1971. Table 3 indicates surface water criteria for public
water supplies (6).
Conventional water treatment as commonly used in this country includes
coagulation using alum, ferric sulfate, or other chemicals as necessary,
but without coagulant aid or activated carbon, sedimentation (6 hours or
less), rapid sand filtration, and disinfection with chlorine without
consideration to concentration or form of chlorine residual.
Table 4 shows the current status of treatment capabilities for all the
substances listed in the 1962 Public Health Service Drinking Water
Standards (1).
Conventional water treatment processes are not effective in the removal
of many organics (as represented in the carbon chloroform extract), chlo-
rides, flourides, nitrates, odor, phenols, sulfates, or total dissolved
solids. To some extent, the concentrations of some heavy metals such as
lead, arsenic, cadmium and mercury are reduced during conventional treat-
ment, but the effectiveness of the processes is unpredictable and there-
fore unreliable.
In those plants where water softening by chemical precipitation is prac-
ticed, the removal of heavy metals is enhanced but often incomplete.
Activated carbon will remove most of the organics and odor. Other special
treatment processes are available for the removal of arsenic, fluoride,
iron, and manganese. At present, no reliable processes adaptable to large
water treatment plants are available or known for the removal of barium,
cadmium, chromium, lead, selenium, or mercury.
Serious health problems can arise when potential chemical pollutants in
the environment find their way into the drinking water. It is important
to keep in mind that poisoning by any of these substances may be not
only acute, but also chronic. One of the most insidious and difficult-
to-measure chronic effects is the production of cancers.
The metalloid arsenic may find its way into drinking water by various
means, including deliberate placement. Contamination of streams with
arsenical wastes can lead to a percolation of this renowned poison into
ground waters used as a source of drinking water, or water from the
contaminated stream may be pumped directly into a municipal supply. In
some areas, arsenic in the water comes from geologic formations. Ordi-
nary filtration techniques usually are not efficient in the removal of
arsenic; consequently, special means must be employed.
The toxicity of arsenic is well known; the ingestion of as little as 100
milligrams usually results in severe poisoning. Chronic arsenic poisoning
14
-------
Table 2
Health and aesthetic significance of trace elements and compounds In finished drinking water.
1962 "USPHS Drinking Water Standards")
(Limits not found in
Name of Ingredient
Substance
Antimony (Sb)
Beryllium (Be)
Bismuth (Bl)
Boron (B)
Cobalt (Co)
Molybdenum (Mo)
Mercury (Hg)
Nickel (Nl)
Sodium (Na)
Tin (Sn)
Uryanyl ion (U02)
Vanadium (V)
Pesticides
Aldrin
Chlordane
DDT
Uleldrln
Endrln
Heptachlor
Heptachlor epoxide
Lindane
Methoxychlor
Toxaphene
Organic phosphorous
plus carbamates.
such as Parathion
Malathlon Carbaryl
and others
Herbicides
Alglcide
Copper key-El
Cuprose
Cutrine
Diquot
Dalapon
2,4-D
2,4,5-T should not
be used.
Mlcro-gard PR
Mogul algictde Ag-470
Radapon
Sllvex (2,4,5-TP)
Tordon 10K & 101
Twlnk
Ureabor
* National Community Water
t Late data from BWII, USPIIS
Health or Aesthetic Effect
Similar to arsenic but less acute. Recommended
limit not to exceed 0.1 mg/1; routinely below
0.05 mg/1; over long-time periods below 0.01
mg/1.
Poisonous in some of its salts in occupational
exposure .
A heavy metal in the arsenic family — avoid in
water supplies.
Ingestion of large amounts can affect central
nervous system, and protracted ingestion can
cause borlsm.
Beneficial in small amounts; about 7 ug/day.
Necessary for plants and ruminants. Excessive
iutak.es may be toxic to higher animals; acute
or chronic effects not. well known.
Continued ingestion or large amounts can damage
brain and central nervous system.
Hay cause dermatitis in sensitive people; doses
of 30-73 mg of NiSOi,*6H20 have produced toxic
effects.
A beneficial and needed body element, but can be
harmful to people with certain diseases.
Long used in food containers without known
harmful effects.
May cause damage to kidney's.
Some evidence that vanadium may be beneficial
with respect to heart disease.
One or all of these complex organic compounds
have severe, acute, adverse health effects
when ingested in large amounts. Small
amounts accumulate, and long-range effects
are generally unknown.
The organic phosphorous and carbamate pesticides
are severe acute poisons affecting the central
nervous system; ingestion of small amounts over
A group having toxic properties of a generally
lower order than the above pesticides. How-
ever, they should not be used without great
care and should not be found in drinking
water.
Supply Study. 2500 samples.
Unofficial
ag/1
0.05
None
None
1.0
None
None
0.005
None
-.
20*
None
5.0
None
0.017**
0.033** .
0.042**
0.017**
0.001**
0.018**
0.018**
0.056**
0.035**
0.005**
O.ltt
1.0
1.0 (Cu)
1.0 (Cu)
1.0 (Cu)
0.2
0.1
1.0
0
1.0
0.1
0.2
o
0.2
1.0 (as B)
Occurrence In U.S.
Water Supplies
mg/1
Average Range
0.069 0-3.28*
0.002 0.0-0.019*
0.000 0. 000-0. 033t
0.005 0.0-0.072*
4« above 0.4-1.9005
20 mg/1
160 samples
in NCWWS
showed
lower
values
• than the
limits.
Same as for
pesticides.
J The amount at, and above, which people on strict (500 mgd) sodium-restricted diets must Include in their dally
sodlum-lnt.'ikc calculatlonn.
i Survey of over 2,000 U.S. municlpallClCH by USPIIS In 1963-66.
** Report of the Committee on W.-iter Quality Criteria, KWl'CA, U.S. Department of the Interior.
tt As parathlon equivalent In cliol inesterase Inhibition.
15
-------
Table 3
Surface water criteria for public water supplies.
Constituent or Characteristic
Permissible
Criteria
Desirable
Criteria
Paragraph
Physical:
Color (color units)
Odor
Temperature*
Turbidity
Microbiological:
Coliform organisms
Fecal coliforms
Inorganic chemicals:
Alkalinity
Ammonia
Arsenic*
Barium*
Boron*
Cadmium*
Chloride*
Chromium*, hexavalent
Copper*
Dissolved oxygen
Fluoride*
Hardness*
Iron (filterable)
Lead*
Manganese* (filterable)
Nitrates plus nitrates*
pH (range)
Phosphorus*
Selenium*
Silver*
Sulfate*
Total dissolved solids* (filterable
Uranyl ion*
Zinc*
Organic chemicals:
j^ $ & *'' *
Carbqn chloroform extract* (CCE)
blue active substances*.
75
Narrative
do
do
Virtually absent
Narrative
Virtually absent
10,000/100 ml1
2,000/100 ml1
(mg/1)
Narrative
0.5 (as N)
0.05
1.0
1.0
0.01
250
0.05
1.0
<4 (monthly mean)
<3 (individual sample)
Narrative
do
0.3
0.05
0.05
10 (as N)
6.0-8.5
Narrative
0.01
0.05
250
residue) 500
5
5
<100/100 ml1
<20/100 ml1
(mg/1)
Narrative
<0.01
Absent
do
do
do
<25
Absent
Virtually absent
Near saturation
Narrative
do
Virtually absent
Absent
do
Virtually absent
Narrative
do
Absent
do
<50
<200
Absent
Virtually absent
0.15
0.20
0.5
Virtually absent
0.017
0.003
0.042
0.017
0.001
<0.04
Absent
Virtually absent
Absent
do
do
do
do
do
do
do
do
do
do
do
do
do
(pc/1)
<100
<1
<2
6
7
8
8
9
8
8
8
8
10
11
12
8
8
8
13
14
15
8
8
8
16
17
8
18
8
19
20
21
21
21
21
21
21
21
21
21
21
8
21
8
constituent.
upon an adequate number of samples. '
does not exceed the specified
resort to even lower concentra-
-------
Table 4
Treatment capabilities for trace elements and compounds.
Essentially
Controlled by no removal by Special
conventional conventional treatment
Substance treatment treatment available
Alkyl benzene sulfonate X
Arsenic X
Barium1
Cadmium1
Carbon chloroform extract X X
Chloride X
Coliform organisms X
Chromium (hexavalent)1
Color X
Copper1
Cyanide1
Fluoride X X
Iron X
Lead1
Manganese X
Nitrate X X
Odor X X
Phenol XX
Radioactivity X
Selenium1
Silver1
Sulfate X
Total dissolved solids X
Turbidity X
Zinc1
Mercury1
1 These elements are removed by conventional treatment to varying degrees.
Unfortunately the degree of removal for different quality waters is un-
predictable.
Coagulation, followed by settling and filtration is effective in
removing turbidity, color, and to some degree bacteria, since many of
these microorganisms are attached to the particles of turbidity. Coagu-
lation and filtration, in removing suspended particles from the water,
also render the water more responsive to disinfection agents.
17
-------
is insidious in onset. The first symptoms are those that may attend
many disorders. They consist of weakness, languor, anorexia, nausea,
vomiting, and diarrhea or constipation. As poisoning progresses,
symptoms become more characteristic, such as conjunctival congestion
and catarrhal inflammation of the upper respiratory tract. Stomatitis,
salivation, dermatitis, and hyperkeratosis may be observed. Liver
involvement may lead to jaundice and eventually to cirrhosis. The
kidneys are also damaged. Evidence of an effect on the capillary beds
is indicated by the edema that occurs. The advanced stages of chronic
intoxication are encephalopathy and peripheral neuritis. Severe blood
dyscrasias are observed also in chronic arsenic poisoning.
The U.S. Public Health Service Drinking Water Standards of 1962 set a
limit of 0.01 milligram of arsenic per liter in drinking water, with
0.05 milligram per liter as a rejection limit if other sources cannot be
found.
For some time, the heavy metals have been a source of concern from a
public health standpoint. Lead exemplifies this problem. Lead taken
into the body can be seriously injurious to health, even lethal, if
taken for either brief or prolonged periods. Prolonged exposure to rel-
atively small quantities may result in serious illness or death. Lead
is a cumulative poison and is dangerous when taken into the body even in
relatively small quantities.
Three fairly distinct types of chronic lead poisoning are described: 1)
the gastrointestinal, 2) the neuromuscular, and 3) the central nervous
system (CNS) syndromes. They may occur separately or in combination.
The neuromuscular and CNS syndromes tend to result more from intense ex-
posure to lead, whereas the abdominal syndrome tends to develop from a
very slow and insidious intoxication. The CNS syndrome is seen typically
in children and is manifested by encephalopathy, visual disturbances, and
eventually brain damage. Also, lead interferes with the normal permea-
bility of the red blood corpuscles. Neuromuscular involvement is
characterized by muscle weakness and fatigue; whereas, the gastrointes-
tinal symptoms are nausea, vomiting, constipation, and a persistent
metallic taste.
It is not uncommon to find the lead content of water in urban supplies
to be in the microgram range of concentration, provided the water is not
stored in tanks painted with oil-base lead paint and provided the pipes
are not of lead or lead alloy. Principal sources of lead in drinking
waters are lead pipes and goosenecks in houses and plumbing systems. The
use of lead pipe is permitted to this date by many plumbing codes. The
sources of lead are varied. In a case in New Orleans in 1959, ice used
for mixing alcoholic beverages was kept in a lead-bottom container; one
serious case of chronic lead poisoning was diagnosed. In New England,
in years past, lead pipes were used to bring acid spring water to farms,
and cases of lead poisoning resulted.
A lead concentration of 0.05 milligram per liter is the limit set by the
U.S. Public Health Service Drinking Water Standards of 1962.
18
-------
Cadmium is recognized as an element of high toxic potential. This metal
is distributed widely in nature and is often used in metallurgy. Cadmium
salts sometimes are used for insecticides and antihelminthics.
Cadmium poisoning of humans has resulted from the consumption of foods
and liquids prepared and left in cadmium-plated containers. As a result,
several health departments have forbidden the use of cadmium-plated food
containers and pipes. Cadmium-contaminated ice cubes in cold drinks have
caused acute gastritis symptoms within one hour; consumption of cadmium
salts causes cramps, nausea, vomiting, and diarrhea. Oral ingestion of
cadmium has been reported as the cause of a number of human deaths.
Cadmium tends to concentrate in the liver, kidneys, pancreas, and thyroid
of humans and animals. Once it enters the body, it is likely to remain.
Normally, many plant and animal tissues contain about 1 milligram of cad-
mium per kilogram of tissue, but there is no evidence that cadmium is
biologically essential or beneficial.
Humans have become ill from ingestion of cadmium in concentrations of 13
to 15 milligrams per kilogram in popsicles, 67 milligrams per liter in a
cold drink, and 530 milligrams per kilogram in gelatin. As little as
14.5 milligrams of cadmium taken orally has caused nausea and vomiting;
yet, in another instance, as much as 330 milligrams has not caused per-
manent injury. Four members of a family whose drinking water contained
0.047 milligram of cadmium per liter had no history of adverse effects.
The 1962 Drinking Water Standards of the U.S. Public Health Service set
a mandatory maximum limit for cadmium of 0.01 milligram .per liter.
Of the many organic water pollutants, dyes and their breakdown products
make up a substantial part. Those dyes that are hydrophilic, non-polar,
and most resistant to breakdown are most likely to reach the drinking
water of various rural and urban communities. The type and concentra-
tion of dyes found in any particular waterway will depend primarily upon
the types of industries along its banks. Most of the dyes in streams
are industrial waste products; some, however, have been placed there for
the purpose of studying the streams.
Several of the dyestuffs identified have been shown to be carcinogenic;
consequently, they create a public health problem. Many times the dyes
have a built-in safety factor because in high concentrations, they turn
the water a characteristic color visible to the naked eye. At low con-
centrations and under conditions of chronic exposure, these substances
may constitute a threat to the water consumer. Other than data concern-
ing the carcinogenic property of the substances, relatively little chron-
ic toxicity data are available. Webb and his co-workers (7) demonstrated
that the chronic oral administration of Rhodamine B (a dye used in water-
flow studies) impaired growth and affected the liver of rats. Dyestuffs,
such as diamineazobenzene and Bismark Brown (both industrial waste prod-
ucts) are highly toxic materials; in rural or municipal drinking waters
they can cause many adverse reactions in the population. To date, no
official limit has been set for the concentration of these chemicals in
drinking water.
19
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Pesticides are high on the list of chemicals beneficial to mankind.
Their contributions to the productivity, improved comfort, and better
health of the people are matched only by their toxic potential. Pesti-
cides are categorized generally into three chemical groups: 1) the
inorganics, comprising the arsenicals, mercurials, and fluorides; 2) the
synthetic organics consisting of the chlorinated hydrocarbons, organic
phosphates, and thiocarbamates, and 3) the natural organics, of which
rotenone, pyrethrum, and nicotine are examples.
Pesticides may gain access to ground and surface waters through direct
application, through percolation and runoff from treated areas, and/or
through drift during application. Pesticides have entered the drinking
water system accidentally when a reverse-pressure system existed. For
example, a worker placed a water hose in a tank partially filled with
chlordane concentrate without realizing that the water had been turned
off at the main valve. The result was a siphoning of the pesticide into
the distribution system. Gross over-application of pesticides is a
common practice that augments the pollutional effects of pesticides to
a considerable extent. These substances are entering our natural waters
in ever increasing amounts.
When considering pesticidal pollution of water, toxicity is not the only
concern. Difficult problems are posed also by tastes and odors. Some
synthetic organics cause highly objectionable tastes and odors, as do
many of their solvents.
The addition of synergists and/or adjuvants to make a particular pesti-
cide more effective has been practiced by the pesticide manufacturing
industry for many years. A marked synergistic effect, or potentiation,
of up to fiftyfold in acute toxicity exists when some chemicals are
administered simultaneously. Such effects cause an increased hazard to
the health of individuals exposed to such preparations.
Each pesticide produces its own pattern of symptoms. Those most studied
are the symptoms associated with organic phosphates and with chlorinated
hydrocarbons. All of the symptoms observed with organo-phosphorus poi-
soning are referable to the inhibition of the enzyme acetylcholinesterase
and the consequent continuous action of acetylcholine on the receptor
neurons. Involuntary salivation, lacrimation, urination, and defecation
along with muscle fasciculation are characteristic of poisoning by organ-
ic phosphorus insecticides. In contrast, the symptoms of poisoning
produced by chlorinated hydrocarbons are loss of appetite and weight,
emaciation, hyperirritability, tremors, convulsions, and coma; death,
if it occurs, is by respiratory failure. Because these effects occur
.when relatively low concentrations are involved, and because there may
be potentiation of toxicity, these chemicals are considered very hazar-
dous, and all precautions should be taken to ensure that toxic concentra-
tions are not introduced into the drinking water.
In conclusion, Dr. Berny Bergen of the University of Massachusetts has
recently reiterated some questions which should be of immediate concern
to us all. These are:
1. What are the long-term toxic and carcinogenic implications
20
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of repeated exposure through drinking water to organics of
industrial origin?
2. What are the toxic implications for the long term of trace
metals occurring in drinking water, and how may these be
controlled?
3. How can water treatment plants reliably destroy viruses in
sources of supply?
4. Are the Public Health Service drinking water standards ap-
plicable to waters derived in large part from treated sew-
age?
5. What are the public health implications of deterioration
of distribution systems at a time when these are being sub-
jected to increasing use?
References Cited
1. Public Health Service, DHEW Publication #956. 1962. Drinking Water
Standards.
2. Hearings before the Committee on Commerce, United States Senate, 92nd
Congress, Second Session, Serial No. 92-57.
3. Journal AWWA, Volume 63, November 1971.
4. Hearings before the Subcommittee on Public Health and Environment,
House of Representatives, Serial No. 92-24.
5. Tardiff, R. G. and L. J. McCabe. September 1968. Rural Water Quality
Problems. Public Health Service.
6. Report on the Committee on Water Quality Criteria. FWPCA - USDI -
April 1968.
7. Webb, J.M., W. H. Hansen, A. Desmond, and 0. G. Fitzhugh. 1961. Tox.
and Appl. Pharmacol. 3:696-706.
21
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22
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, MERCURY AS AN ENVIRONMENTAL POLLUTANT
Michael G. Petit
Introduction
There has been growing concern in recent years about toxic levels of
environmental chemicals observed in natural substrates. In many
instances, the element mercury is implicated as a pollutant (5) and
the source can be traced to man's industrial or agricultural activity
in the area. These instances represent examples of local pollution by
mercury and are relatively easy to control once the sources are located.
Of even greater concern is the problem of locating those sources of
environmental mercury from which the effluent mercury has a more
generalized distribution. These sources are more difficult to define
because mercury from this source appears as a background level in
substrates of broad general geographic distribution. This raises the
important question: Are there any controllable sources which discharge
mercury into a situation capable of providing a generalized geographical
distribution? The answer to this question depends upon two factors:
the nature of the effluent and the transport systems available for
distribution.
Early work by Moruzumi et. al. (3) using stratified annual ice sheets
near Camp Century, Greenland, demonstrated that lead was a pollutant of
global distribution. More recently, Weiss et. al. (6) extended the
analysis of the ice sheets to include mercury. Their analytical results
strongly suggest that mercury pollution is also of global distribution.
These workers examined all known man-made sources of atmospheric mercury
and found that the sum total of man's contribution was only a fraction
of the total annual atmospheric burden. They suggested that natural
degassing of the earth's crust and upper mantle was the major source of
atmospheric mercury and that activities of man resulting in alteration
of terrestrial surfaces must be included as a passive source of atmos-
pheric mercury.
Environmental Substrates
If this is true, such geological processes as glacial movements followed
by recession of the ice sheets should have resulted in the release of
tremendous quantities of mercury into the atmosphere and, indeed, may
still be. To examine this point further, it would be necessary to have
access to an environmental substrate whcih was deposited during the
Pleistocene and for which there exists a continuous or semicontinuous
record extending into modern times. Although the chances of finding
such a substrate which has remained essentially constant in composition
since deposition are remote, guano deposits of the Mexican free-tailed
bat Tadarida brasiliensis represent a close approximation.
Deposits of this material occur in dry solution type caves in the Amer-
ican Southwest and in volcanic tubes in tropical and temperate zones of
worldwide distribution. Archeological sites such as the Anasazi ruins
in Canyon de Chelly National Monument which are located in rock shelters
and, as a result, are not exposed to weathering provide sources of
material such as woodrat scat (Neotoma sps.) which can be accurately
23
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dated. Although this type of substrate is relatively modern, it was
deposited well before the industrial revolution. Thus, these deposits
provide us with a substrate which is suitable for determining baselines
for environmental chemicals. This work reports results obtained from a
dry cave (Eagle Creek Cave (2), 33°01' N lat, 109°25' W long) housing a
large colony of the Mexican free-tailed bat, ' Tartarida brasiliensis.
Experimental
Three 6" diameter core samples were extracted from the guano deposits
on the floor of the cave directly underneath the large vertical crack
in the ceiling which extended up fifty feet or more into the ceiling.
Workers wore coveralls and were outfitted with breathing apparatuses
in order to protect the worker and minimize sample contamination. The
core samplers were percussion driven steel tubes previously coated with
plastic. The deposits directly under the crack were five feet, four
inches deep and represented sixteen years' accumulation of guano. This
cave had been previously mined for its guano deposits (mined to bedrock
in 1954) and as a result, the age of the bottommost layer was accurately
known. After the core sampler was driven down to bedrock, a trench was
dug to expose the length of the core. The core was then removed and
the ends sealed with sheet plastic and paraffin. The cores were then
wrapped in 3" foam rubber and immediately transported to our laboratory
for dating and analysis.
Once in the laboratory, the cores were placed in a horizontal die and
the top half of the core sampler casing was cut away with a dental drill,
exposing one half of the cylindrical guano core. Since there was some
vertical mixing at the core sampler/guano interface, the top half of the
exposed guano was mechanically removed by vacuum down to the center of
the core. The core was then dated by a stratigraphic method described
elsewhere (1).
After the annual layers were defined and dated, they were extracted with
an acid washed ceramic spatula and transferred to 250 ml erlenmeyer
flasks with 24/40 stoppers for weighing. Approximately one gram samples
were digested with 25 ml of either 1:1:2 HNC^I^SO^I^O or 42:4:4
HNC>3:H20 for 20 hours in a 40°C shaking water bath. Five percent
was added periodically to insure oxidation of the mercury during diges-
tion. The samples were then removed from the water bath and cooled.
Five additional milliliters of 5% KMn04 were added to each flask, 2 ml
of potassium perchlorate and 2 ml of hydroxylamine hydrochloride com-
pleted the pretreatment. The samples were analyzed in five duplicate
lots by cold vapor atomic absorption on a single beam Norelco Unicam
Atomic Absorption spectrometer and a Laboratory Control Data double beam
analyzer. The averaged results of five analyses are shown in Figure 1.
Discussion
Figure 1 shows a general zigzag pattern in the mercury concentrations
found in consecutive years. It is also apparent that concentrations
reached a relative maximum in 1957 and showed a large decrease in 1958
and 1959 and, in subsequent years, did not return to the high levels
24
-------
Figure (1). Chronological record of mercury concentrations
found 1n guano deposits of the Mexican free-
tailed bat Tadarida braeilieneis recovered
from the dry cave in Eagle Creek Canyon,
Greenlee County, Arizona.
J
LD
Lf)
en
CO
LO
cr>
en
LO
O
ID
UD
CM
<£>
in
CTi
ir>
. cr>
CO
vo
en
o
r~-
en
25
-------
140--
130"
Cu
(thousands
of tons)
Figure 2. Annual copper production of smelter located
5.5 airmiles from the bat cave at Eagle Creek,
Year
26
-------
observed in 1957 until 1971. Figure 2 shows the annual copper production
of the nearby copper smelter. Gopper production decreased in the years
1957, 1958, and 1959, due in part to strikes at the plant. After a grad-
ual recovery, the copper workers' strike of 1967 again depressed copper
production until 1969 when copper production was back to normal. There
is a one year delay observed between the decrease in copper production
and the decrease in mercury in the food chain of the free-tailed bat,
which implies an indirect route of entry into this mammal's food chain.
If the animals were ingesting mercury in their drinking water, there
should be no delay observed because the bats are present in the area
during the rainy season at Eagle Creek when scrubbing of mercury from
the air by rain should be maximal. This delay suggests that the mercury
is taken up from the atmosphere either directly or from precipitation at
a lower level on the food chain. Since the staple in this bat's diet is
microlepidoptera (4), it is reasonable to suspect either the moth larvae
or the vegetation they feed on as the port of entry into the bat's food
chain. A more extensive investigation of the transport system of mercury
into and through the food chain of the free-tailed bat is needed.
Conclusion
Fluctuations in atmospheric levels of mercury are observed in annually
deposited guano of the free-tailed bat which correlate with copper
production in the area. This substrate provides a unique chronological
record of the extent of mercury pollution in an area. Thus, it has
potential uses as an indicator substrate for evaluating the effectiveness
of clean-up or pollution abatement procedures. Since this substrate is
deposited in dry caves, it is not subject to leaching by percolating
ground water. It may be useful for assessing the impact of recent
geological phenomena, as well as soil tillage (surface altering activ-
ities), on levels of environmental chemicals.
References Cited
1. Altenbach, J. S., and M. G. Petit. 1972. A stratigraphic dating
technique for guano deposits of the Mexican free-tailed bat. J.
Mamm., in press.
2. Cockrum, E. L. 1969. Migration in the guano bat, Tadarida brasil-
iensis. In Contributions in Mammalogy, p. 303-336. Misc. Pub. #51,
The Museum of Natural History, University of Kansas.
3. Moruzumi, M., T. J. Chow, and C. C. Patterson. 1969. Geochim.
Cosmoclum. Acta. 33:1247.
4. Ross, A. 1961. Notes on the food habits of bats. J. Mamm. 66:42.
5. Van Den Berg, L. A. 1971. Hazards of mercury: sources, distribu-
tion, and control. Env. Res. 4:26-31.
6. Weiss, H. V., M. Koide, and E. D. Goldberg. 1971. Mercury in a
Greenland ice sheet: evidence of recent input by man. Science 174:
692-694.
27
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28
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MOLYBDENUM AS AN ENVIRONMENTAL POLLUTANT
Gerald M. Ward
The official title of the project is "An Interdisciplinary Study of the
Transport and Biological Effects of Molybdenum in the Environment." The
project is supported by the National Science Foundation and the princi-
pal investigators are Dr. Willard Chappell and Dr. Roger Jorden of the
University of Colorado. The individual investigators represent many
disciplines, many departments, and two universities.
The project was initiated because the levels of molybdenum in certain
waterways in Colorado were found to exceed the national average. This
is probably not surprising since Colorado produces about 42% of the
world's supply of molybdenum. The biological effects of molybdenum on
man are essentially unknown but molybdenum toxicity in ruminant animals
has been recognized since 1938. Molybdenum as a contaminant is not
considered as hazardous as some other heavy metals such as mercury and
lead but, unlike these elements, it has a much higher biological avail-
ability; it is more readily absorbed from the intestinal tract.
This project was designed to study the sources, transport and availability
of molybdenum to man on the Eastern Slope of the Rocky Mountains in Colo-
rado.
It was early established that the principle source of molybdenum was the
Climax molybdenum mine at Climax, Colorado. The drainage from this mine
area is through the Ten Mile Creek to Dillon Reservoir. Water from
Dillon Reservoir is taken through the Roberts Tunnel under the Continent-
al Divide into the South Platte River in order to augment the water
supply for Denver. The South Platte flows through Denver and on through
the farming areas around Brighton and Platteville where it furnishes
irrigation water. Water from Dillon Reservoir is used intermittently
and distribution to Denver residents depends upon their location in the
city. The normal flow from Dillon Reservoir is through the Blue River
to Kremmling and into the Colorado River.
Another source of molybdenum in the Denver Metropolitan area is Clear
Creek which drains the area of another but smaller molybdenum mine near
Empire, Colorado. Clear Creek supplies water to the towns of Golden
and Westminster and irrigated farms in the region.
The relation between mining activity and the concentration of molybdenum
in water is supported by the numbers below which, although maximum values
in some cases, are representative of the situation found in Colorado.
Ten Mile Creek 3,800 grams/liter
Dillon Reservoir 300
Blue River 240-430
Denver Water (from Dillon) 190
Denver Water (other sources) 2
Golden, Westminster Water 250-580
Mean United States Water Supply 0.35
29
-------
It is clear that there are great differences in molybdenum concentration
in water associated with mining and milling. It has been demonstrated
that such high levels in streams are associated with human activity.
Streams draining undisturbed areas of known molybdenum deposits have
normal molybdenum levels.
Biological Effects
The biological effects of excess molybdenum were first described in
England for sheep and cattle in 1938. In 1941, symptoms of molybdenum
toxicity in cattle were described in the Blue River Valley where grazing
cattle on irrigated meadows is the general practice. The clinical
symptoms in cattle are severe diarrhea, poor appetite, and a gray or
rusty coat color on dark colored animals. Osteoporosis has also been
described in cattle. Molybdenum toxicity apparently results from a
relative copper deficiency. Ruminants are 100 to 200 times more sensi-
tive to molybdenum than non-ruminants such as horses, swine, poultry,
or rats and presumably humans although we have no information.
The mechanism by which excess molybdenum intake causes a copper defi-
ciency in ruminants is not understood. One suggestion is that a
biologically inactive molybdenum/copper complex is formed thereby re-
ducing the availability of copper. The level of sulfate in the diet is
also an important factor because a high sulfate intake will cause a
reduction in molybdenum uptake. Molybdenum is a structural component
of the enzymes xanthine oxidase and aldehyde oxidase. These enzymes are
required for uric acid metabolism and speculation would suggest a possi-
ble relation to gout.
Research Flan
The flora and fauna of the alpine regions is being sampled as well as
the soluble and particulate material in the water courses. Comparisons
are made between the molybdenum level in plants, invertebrates, mammals,
and birds found in the undisturbed and in the mining areas.
A detailed study of molybdenum concentrations in the water and biota in
Dillon Reservoir is underway because a marked seasonal turnover has been
observed. The highest levels are found at the bottom during summer and
the water for Denver is withdrawn at this level. The layering phenomenon
may have a biological or a physical explanation. An extensive monitoring
system has been set up to measure molybdenum in streams and rivers
draining the mountains of central Colorado.
Agricultural studies are being conducted in the farming regions north of
Denver that are dependent upon irrigation water, some of which contain
the higher levels of molybdenum. Irrigation water, soil samples, and
crops are being analyzed to determine the transfer of the element. It
is known that availability is greater from alkaline than acid soils.
The availability from a variety of soils in this region is being evalu-
ated by greenhouse studies.
30
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Molybdenum is readily absorbed by cattle and appears in milk and as a
result, provides a simple means of evaluating the amount in the feeds
fed to cows. Since the forage fed to milking cows is still produced on
many farms, a good transfer study can be established from irrigation
water to soil to plants to milk,, Preliminary studies indicate a range
of 50 to 150 yg/liter for milk produced in the Denver area with some
indication of higher levels in those areas dependent on irrigation
water with higher molybdenum concentration.
By determining the molybdenum content of other important dietary com-
ponents, it should be possible to estimate the dietary (including water)
intake of average residents of Denver.
Metabolic studies are underway to evaluate the effects of low level
(1-10 ppm) chronic intakes of molybdenum by rats. The effects of
molybdenum on calcium metabolism and osteoporosis is being studied.
Analytical work is, of course, an important phase of this work because
it is necessary to analyze a very large number of samples of diverse
character with speed and precision. Methods under study include wet
chemistry, x-ray fluorescence, and charged particle induced x-ray
fluorescence (using the C.U. cyclotron). Data handling likewise is
essential and is being developed to handle and retrieve all the data
of the project.
An important aspect of the project is developing cooperation with many
public and private agencies.
Public opinion regarding the possibility of molybdenum contamination is
under study. A survey has been conducted to study public perception of
environmental hazards generally and if warranted, a follow-up survey
will be conducted.
The economic impact of molybdenum production of pollution possibilities
and abatement has been prepared.
31
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32
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LEAD IN SOILS AND PLANTS
R. L. Zimdahl and J. H. Arvik
For the past two years, a research project entitled "Impact on Man of
Environmental Contamination Caused by Lead" has been under way at Colo-
rado State University. This project, financed by the RANN (Research
Applied to National Needs) Division of the National Science Foundation,
includes seven faculty investigators and several graduate students and
technicians. The particular portion of the project with which this
paper deals is the transport of lead through soil and its uptake by,
and effect on, plants.
As part of the study of lead transport from a line source, to and
through soil, a site with a traffic volume of 18,000 cars per 24 hours
was selected on Interstate Highway 25, north of Denver, Colorado. We
were interested in learning where lead emanating from automobiles was
accumulating, and the rate of accumulation. The first work utilized a
truck-mounted hydraulic probe to sample the soil in six-inch vertical
increments to a depth of three feet, and in horizontal increments to
approximately 500 feet from the edge of the interstate lanes. The 0 to
6 inch sample analysis (Figure 1) shows that lead concentrations were
highest immediately adjacent to the roadway and concentration rapidly
diminished with depth and distance. Measured lead values for soil
samples obtained further than about 100 feet from the highway were
indistinguishable from background. The baseline or background value of
lead in soil typical of the field site location was determined to be
22.9 ppmw with a standard deviation of 4.4 ppmw (20). This value is
somewhat higher than the world average of 16 ppmw (6). Lead values,
shown in Figure 1, reached 530 ppmw on the east side of the northbound
lane and 370 ppmw on the west side of the southbound lane. Average
traffic flow rates for the two lanes were identical and the lanes were
constructed and opened to traffic at the same time. Preferential build-
up of lead in soil immediately adjacent to the northbound lane was
confirmed by sampling at one-inch intervals from the surface to six
inches. These results are presented in Figure 2. The data in Figures
1 and 2 confirm the observation made by others (2, 4, 11, 13, 17, 19,
24) that lead content decreases with increasing depth and distance from
the highway. The mechanism by which preferential build-up occurs may
involve reinjection of lead particles into the atmosphere from those
originally deposited on the west side of the highway, with subsequent
redeposition on the east side. However, our data do not strongly sup-
port this contention. A second hypothesis was that the prevailing wind
direction might be from the west and account for deposition to the east.
Wind speed and direction records, taken at the site, clearly indicate a
predominant north or northwest wind source. Taken alone, these data
support the finding that more lead is present along the east side of the
highway, but they do not totally account for the unequal distribution.
It is known that load conditions on the automobile can effect lead
emission rates and some preliminary work suggests that a slight rise to
the north may account for the observed differences. That is, the amount
of gasoline a car uses as it goes by a given point or the load under
which it is operating may be as important determinants of lead deposi-
tion as the number of cars going by that point (3, 7, 15).
33
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LO
Lead Accumulation in Soil Adjacent to Roadway
144th St. Exit, Interstate Highway 25, Colorado, October, 1970
Distance West From Pavement Edge, Feet
550
500
450
400
i 350
CO
Q 30°
o>
\ 250
-Q
0-
o. 200
150
100
50
0
i i i i i i
_
Depth: 0-6 inches
-
Fence -*
—
-
• • . .
-° °^d
i i i i i i
300 200 100
<
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/ •*•• ^r
(
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c
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)
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)
ii ii
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-
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*- Fence
-* Irrigation Ditch
:
-
_-.
\,
0
III II
100 200 300
Distance East From Pavement Edge, Feet
Figure 1
-------
LEAD ACCUMULATION IN SOIL ADJACENT TO ROADWAY
144th ST. OVERPASS, INTERSTATE HIGHWAY 25, COLORADO, SEPTEMBER, 1970
o
01
Q_
1400
1200
1000
800
600
400
200
0
LOCATION A
ROADWAY, TOP VIEW
N
LOCATION B LOCATION C
DEPTH IN SOIL, INCHES
B
I
I
••OT
•;•:•
'"I"*
•D
LOCATION D
Figure 2
-------
We were also interested In determining the capacity of the soil to sorb
or immobilize lead. Our first experiment studied the reduction in the
initial activity of radioactive lead (210Pb) sorbed from solution as a
function of time. We found that with San Luis, a fairly sandy soil,
and Weld, a clay loam soil, the sorption equilibrium occurred in about
24 hours. Another experiment measured the rate at which lead was de-
pleted from a lead nitrate solution by four soil types. The sorption
equilibrium occurred in 24 to 48 hours. Knowing this value, we pro-
ceeded to study the sorption of lead by soil. The experiments were
conducted by adding a solution of lead nitrate of known concentration
to a known weight of soil and holding them at constant temperature in
an oscillating water bath for 48 hours. The supernatant liquid was
decanted and centrifuged and a 5 ml aliquot analyzed for lead.
A total of seven different soils have been used in these studies. They
range from soil with 87% sand to a heavy clay soil. The cation exchange
capacity (CEC) varies from 2.5 to 38. A plot of N* (the theoretical
monolayer capacity) derived from the Langmuir sorption equation vs. CEC
shows a positive correlation between the two. The exception to this
generalization is found with soils that deviate markedly from a standard
pH. Initially all of the soils used had a pH near neutrality. Another
soil had a pH of 4.1 and did not fit the correlation between N* and CEC.
We hypothesized that pH could be an operative factor and that raising
the pH would bring N* into line with the other soils. This was done
and our hypothesis verified. Thus, cation exchange capacity is a pri-
mary determinant of the ability of a soil to sorb or immobilize lead
but the effect of exchange capacity is attenuated by pH. As we lower
the pH of the soil less lead is sorbed to the soil and, therefore, may
be more available to plants.
Lead in plants. Our initial studies were designed to measure lead up-
take by plants growing in hydroponic solutions containing lead and in
soils that had been doped with various levels of lead. We hoped to
learn if different kinds of plants took up different amounts of lead and
how much lead a plant could take up when growing in hydroponic culture.
We have also studied the possibility of foliar uptake of lead. Sugar
beets, corn, beans, and wheat grown in soil treated with lead nitrate
take up more lead as the level of lead in the soil increases from ap-
proximately 80 to 2000 ppmw. Sugar beets seem to have a much greater
ability to take up lead than the other three plants. These same plants
have been grown using techniques of hydroponic culture. The plants are
started and grown to a predetermined size in Hoagland's nutrient solu-
tion. They are then placed in a lead solution of known concentration.
We have shown that lead uptake by the plant is directly related to
solution concentration. Further, lead is concentrated in the root with
limited translocation to the shoot. Analysis of pinto bean plants
showed the greatest concentration in the root. The stem often had a
level nearly equal to the root but never higher. The primary leaf was
lower than the stem but always higher than the first trifoliate leaf.
These observations held regardless of the beginning lead concentrations.
Table 1 shows lead uptake from solution by four plants. These data
indicate that massive amounts of lead can be absorbed by a plant. It
is also of interest to note that the ratio of the amount in the root to
36
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that in the shoot decreases with increasing solution concentration.
Limited translocation from root to shoot has been reported (8, 9, 10,
21, 22). These data indicate limited translocation under most condi-
tions and that roots have a limited capacity to bind and hold lead.
With higher solution concentration, translocation of lead is increased
and the concentration in the shoot increases. The data indicate, but
do not prove, that lead uptake may be a passive process or that lead
may affect root cell membrane permeability. If the latter is true ex-
ternally, it could also be true internally and account for the trans-
location seen with increasing concentration. We intend to explore this
in greater detail.
TABLE 1
Lead Uptake from Solution by Four Plants
yg/g Dry Weight Absorbed from Pb(NO,)?
Plant and Part - - ?-=-
100 ppm Root/Shoot 1000 ppm Root/Shoot
Pb Ratio Pb Ratio
Pinto bean root
shoot
Sugar beet root
Wheat root
shoot
Corn root
shoot
32,400
140
54,300
9,300
260
10,600
390
231.4
35.8
27.2
54,400
13,300
84,800
16,000
5,800
22,700
9,160
4.1
2.8
2.5
One of our objectives has been to resolve the controversy in the liter-
ature concerning the site of lead uptake by the plant. Citations are
available to support root (1, 14, 21, 23) or shoot (foliar) (5, 18, 19)
uptake. Our work has shown that root uptake does occur. No reports
have separated the supposition of foliar uptake from the possibility
that lead may exist as a topical coating which may become embedded in
or fixed to waxy leaf cuticles (12, 19). Two experimental techniques
have been developed to study the problem. In the first, an exposure
chamber with a square cross-section and a removable top and bottom was
fabricated from V' plexiglass.
A lead aerosol is generated by aspirating a water solution or suspension
of a chosen lead salt through 3" x 8" quartz glass chamber which is
wrapped with resistance heating tape and insulated by V asbestos. The
tape is connected to a variable output transformer which allows adjust-
ment of the chamber temperature. Air pressure for aspiration is provided
by a laboratory vacuum pump. The aerosol is flash evaporated at 325 C
in the heating chamber and driven through an 18" water cooled condenser
to remove the water vapor. A portion of the lead salt remains suspended
in the air stream as a particulate and is introduced to the plexiglass
exposure chamber. The aerosol is composed of particles measuring less
than 1 y, simulating conditions existing downwind of heavily-travelled
highways (7).
37
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Plants grown in commercial vermiculite irrigated with Hoagland's
solution are placed in the exposure chamber. Vermiculite was chosen
to permit more efficient cleaning of plant roots following treatment
and to prevent the possibility of lead uptake from soil. The surfaces
of the pots are protected from lead settling on them by putting on a
layer of soil with a high sorptive capacity for lead. The pots are
placed on a layer of the same soil in the bottom of the chamber. This
isolates the roots above and below a layer of soil. Therefore, any lead
which gets in the plant must come from foliar exposure. Considerable
work has been done to develop this technique and determine optimum
operating temperature, flow rates, particle size, and lead aerosol con-
centration. The method does offer great promise for specific foliar
exposure. However, this technique alone will not permit us to determine
if lead is in the plant or on the plant. In conjunction with other
procedures, it will allow the study of foliar penetration of lead.
We recognize the possibility of stomatal penetration but do not consider
it an important route of entry for particulates. The primary barrier
for materials to enter the plant leaf is the cuticle, and if lead is
taken into the plant through the foliage, it must first pass through
that structure.
To approach the problem of cuticular penetration, we have modified the
methods of Orgell (16) and Yamada (25). A 3% solution of pectinase
(Rohm & Hass Pectinol 10-M) or cellulase-hemicellulase mixture (R & H
HP-150 concentrate) is prepared in deionized water and adjusted to pH 3.
Leaf discs are vacuum-infiltrated with the solution and agitated gently
in a reciprocating water bath at 30 C for 24-72 hours. The enzymes
remove the upper and lower cuticles from the leaves, as a plant leaf is
basically a sandwich of cells and vascular tissue held together by
pectins, and having its surface covered by a waxy cuticle. Fruit discs
serve as well to provide a cuticle for penetration studies. After re-
moval from the discs, the cuticles are examined microscopically to
insure that no physical damage has occurred. They are then washed in
deionized water and fixed with silicone adhesive across the open end of
a 15 x 100 mm polypropylene test tube. Five ml of deionized water is
introduced into the tube through a small hole in the opposite end. This
tube is then partially immersed in a larger polypropylene test tube con-
taining 25 ml of 100 ppmw solution of lead salt. The tubes are adjusted
to prevent hydrostatic pressure on the membrane. After 144 hours at
30°C in a stationary water bath, the lead concentration in the two test
tubes is measured. Experiments have been conducted on Philodendron
leaf, apple, tomato, and pepper fruit cuticle. Even under the extreme
conditions of high lead concentrations and long exposure times, far less
than 1% of the lead in the larger test tube is able to penetrate the
cuticular barrier. These data question the assumption of foliar uptake
of lead and we anticipate that the plants exposed to an aerosol will
support this contention.
In summary, our work to date does not indicate imminent hazard from en-
vironmental contamination of soils and crops by automotive lead. However,
the margin of safety is not reassuring, and there are definite indications
that less dramatic effects do occur in man.
38
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References Cited
1. Berger, K. C., W. H. Erhardt, and C. W. Francis. 1962. Polonium-210
analyses of vegetables, cured and uncured tobacco, and associated
soils. Science 150:1738-1739.
2. Cannon, H. L. and J. M. Bowles. 1962. Contamination of vegetables
by tetraethyl lead. Science 137:765-766.
3. Daines, R. H., H. Motto, and D. M. Chilko. 1970. Atmospheric lead:
its relationship to traffic volume and proximity to highways. Env.
Sci. and Tech. 4:318-322.
4. Dedolph, R., G. Ter Haar, R. Holtzman, and H. Lucas, Jr. 1970.
Sources of lead in perennial ryegrass and radishes. Env. Sci. and
Tech. 4:217-223.
5. Francis, C. W. and G. J. Chesters. 1967. Radioactive ingrowth of
polonium-210 in tobacco plants. J. Agr. & Fd. Chem. 15:704-706.
6. Goldschmidt, V. M. 1937. The principles of distribution of chem-
ical elements in minerals and rocks. J. Chem. Soc. (London) 655-673.
7. Habibi, K. 1970. Characterization of particulate lead in vehicle
exhaust—experimental techniques. Env. Sci. and Tech. 4:239-248.
8. Hammett, F. S. 1928. Studies in the biology of metals. Frotoplasma
4:183-186.
9. Hevesy, G. 1923. The absorption and translocation of lead by
plants. Biochem. J. 17:435-439.
10. Kloke, A. and K. Riebartsch. 1964. Contamination of crop plants
with lead from motor vehicle exhaust gases. Naturwissenschaften
51:368-369.
11. Lagerwerff, J. V. 1967. Heavy metal contamination of soils. In
Agriculture and the quality of our environment, pp. 343-364. Amer.
Assn. for Adv. Sci. Pub. #85. Washington, D.C.
12. Lagerwerff, J. V. 1.971. Uptake of cadmium, lead, and zinc from
soil and air. Soil Sci. 111:129-133.
13. Lagerwerff, J. V. and A. W. Specht. 1970. Contamination of road-
side soil and vegetation with cadmium, nickel, lead, and zinc.
Env. Sci. and Tech. 4:583-588. t . ' .
14. Martin, G. C. and P. B. Hammond. 1966. Lead uptake by bromegrass
from contaminated soils. Agron. J. 58:553-554.
15. Motto, H. L., R. H. Daines, D. M. Chilko, and C. K. Motto. 1970.
Lead in soils and plants: its relation to traffic volume and
proximity to highways. Env. Sci. and Tech. 4:231-237.
i
16. Orgell, W. H. 1955. The isolation of plant cuticle with pectic
enzymes. PI. Physiol. 30:78-80?.
17. Page, A. L. and T. J. Ganje. 1970. Accumulations of lead in soils
for regions of high and low motor vehicle traffic density. Env.
Sci. and Tech. 4:140-142.
39
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18. Ruhling, Xke and G. Tyler. 1968. An ecological approach to the
lead problem. Botaniska Notiser 121:321-342.
19. Schuck, E. A. and J. K. Locke. 1970. Relationship of automotive
lead particulates to certain consumer crops. Env. Sci. and Tech.
4:324-330.
20. Seeley, J.>L., D. Dick, J. H. Arvik, R. L. Zimbahl, and R. K.
Skogerboe. 1972. Determination of lead in soil. App. Spectroscopy
26:456-461.
21. Ter Haar, G. L. 1970. Air as a source of lead in edible crops.
Env. Sci. and Tech. 4:226-229.
22. Ter Haar, G. L., R. R. Dedolph, R. B. Holtzman, and H. F. Lucas, Jr.
1969. The lead uptake by perennial ryegrass and radishes from
air, water, and soil. Env. Res. 2:267-271.
23. Tso, T. C. 1970. Limited removal of 210Po and 210Pb from soil and
fertilizer leaching. Agron. J. 62:663-664.
24. Warren, H. V. and R. E. Delavault. 1962. Lead in some food crops
and trees. J. Sci. Fd. and Agr. 13:96-98.
25. Yamada, Y., S. H. Wittwer, and M. J. Bukovac. 1964. Penetration
of ions through isolated cuticles. PI. Physiol. 39:28-32.
40
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HEAVY METAL POISONINGS IN ANIMALS
Arthur A. Case
Abstract
Heavy metal poisoning in animals is produced by overexposure to
antimony, cadmium, chromium, cobalt, copper, iron, lead, mercury,
molybdenum, nickel, thallium, tin, and zinc. Animals are usually
exposed by eating or drinking the toxicant which contaminates their
food or water. The term poisoning usually means acute or chronic
intoxication leading to death of serious disturbance of health.
Low grade metabolic disturbance of growth, nutrition, and reproduction
may be economically more important than the frank intoxications as
such. Poisoning may be due to deliberate malicious action of man but
is more likely to occur from errors in the use and management of
poisons, improper waste disposal or storage of toxic substances, or
ignorance regarding the presence of toxic chemicals in the environment.
Recent instances of metabolic disturbances in cattle due to the
imbalance of natural trace or major elements in the flood plains below
mining or other earth-moving operations have occurred in Missouri.
Similar situations are possible in drainage areas below surface dump
areas or where toxic substances may be applied in one area and wash
onto other places during heavy rainfall. The toxic substances are
deposited in the flood plains by the flood water and are then taken up
by the vegetation growing in the area.
Heavy Metal Poisonings in Animals
Intoxications caused by overexposure to heavy metals are not included
as legally reportable conditions. Data have to be based on personal
experience to a large extent (1) or on reports such as recent papers
by Aronson (2), Buck (5), and Zook (17, 18) concerning lead poisoning.
More animals are poisoned by lead than any other heavy metal according
to recent reports (1, 2, 5, 17, 18). Lead compounds are commonly
included in paint, putty, glazing compounds, plumbing fixtures, motor
fuels; and there are many other sources which make lead the heavy
metal most likely to. be available in the environment.
Antimony is found in certain kinds of paints and enamels and certain
medical agents. Both cadmium and chromium are electroplating metals
and may be associated with other metal refining processes. Mercury
has wide use in industry and is still in use as a fungicide under certain
circumstances.
Thallium is a dangerous and widely distributed rodenticide now withdrawn
from approved use, but still widely available in certain areas. Zinc
may be an industrial hazard and with certain other elements (zinc phos-
phide) can be a dangerous toxic hazard to any kind of animal and man.
-------
Low grade metabolic disturbance of growth, nutrition, and reproduction
may be of greater economic significance than losses from the more
dramatic acute lethal intoxications in cattle (1, 3, 4, 6, 9, 10).
Barshad (3) described a copper-molybdenum imbalance in cattle in Cal-
ifornia. Britton and Goss (4) worked with chronic molybdenum poisoning
in Nevada, and Davis (8) encountered a complex imbalance under Florida
conditions which also involved interrelationships with phosphorus,
copper, and molybdenum. Church (7) cites normal relationships of the
major and trace elements as well as imbalance and the effect of such
on ruminant nutrition. Case et. al. (6) and Ebens et. al. (9) have
recently reported complex interrelations of anomalous trace elements
in the geochemical environment associated with drainage from mining
operations in Missouri. Cattle were affected in much the same way as
described for cattle by Fleming '_et. al. (10). In all of the situations
involving an imbalance of copper-molybdenum reported by the authors
mentioned above, the ratios of copper to molybdenum varied considerably
from those ratios given by the National Research Council as normal,
balanced ratios for good health.(12).
Janes et. al. (11) have reported still another interrelationship of
trace elements involved in neoplasia of rabbits and man.
Selby et. al. (13) discussed the effects of trace elements on human
and animal health and their observations agree in general with those
expressed by Schutte (14) and the more recent definitive reference by
Underwood (16).
Thompson et. _a]L. .'(15) mention normal interrelation of both major and
trace elements for cattle, especially Charolais.
In some instances, so many elements, both major and trace, are anomalous
and the interrelationships so complex that it is impossible or imprac-
tical to do other than move the young cattle and breeding stock away
from the contaminated environment to an area that is nearer to a natural
balance of the elements.
References Cited
1. Anonymous. 1968-71. Annual Reports Veterinary Diagnostic Labora-
tory and Veterinary Clinic Records, School of Veterinary Medicine,
University of Missouri, Columbia, Mo.
2. Aronson, A. L. 1972. Lead poisoning in cattle and horses following
long-term exposure to lead. Am. J. Vet. Res. 33(3):627-629.
3. Barshad, I. 1948. Molybdenum content of pasture plants in relation
to toxicity to cattle. Soil Sci. 66(3):627-629.
4. Britton, J. W., and H. H. Goss. 1946. Chronic molybdenum poisoning
in cattle. J.A.V.M.A. 108(828):176-178.
5. Buck, W. B. 1970. Lead and organic pesticide poisoning in cattle.
J.A.V.M.A. 156:1468-1472.
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6. Case, A. A., L. A. Selby, D. P. Hutcheson, R. J. Ebens, J. A.
Erdman, and J. L. Feder. 1972. Metabolic disturbances in young
beef cattle associated with abnormalities in their geochemical
environment. Proceedings of Fifth Trace Elements Conference,
University of Missouri, Columbia, Mo., in press.
7. Church, D. C. 1971. Nutrition (with chapters by G. E. Smith,
J. P. Fontenot, and A. T. Ralston), v. 2, of Digestive Physiology
and Nutrition of Ruminants. Oregon State Univ. Bookstores, Corvallis.
8. Davis, G. K. 1950. The influence of copper on the metabolism of
phosphorus and molybdenum. In Copper Metabolism: A Symposium on
Animal, Plant and Soil Relationships, p. 216-229. Eds. W. D.
McElroy and Gentley Glass, Johns Hopkins Press, Baltimore.
9. Ebens, R. J., J. A. Erdman, G. L. Feder, A. A. Case, and L. A.
Selby. 1972. Geochemical anomalies of a claypit area, Callaway
County, Missouri, and related metabolic imbalance in beef cattle.
U.S. Geol. Survey Prof. Paper, in press.
10. Fleming, C. E., J. A. McCormick, and W. B. Dye. 1961. The effects
of molybdenosis on a growth and breeding experiment. Nevada Univ.
Agric. Exper. Sta. Bui. #220.
11. Janes, J. M., J. T. McCall, and L. R. Elveback. 1972. Trace metals
in human osteogenic sarcoma. May Clinic Proc. 47:476-478.
12. National Research Council. 1970. Nutritional requirements of beef
cattle. Washington, D.C., National Academy of Science.
13. Selby, L. A., C. J. Marienfeld, and J. 0. Pierce. 1970. The
effects of trace elements on human and animal health. J.A.V.M.A.
157(11):1800-1808.
14. Schutte, Karl H. 1964. The Biology of the Trace Elements, their
Role in Nutrition. J. B. Lippincott Co., Philadephia.
15. Thompson, U. D., L. A. Maddox, Jr., and L. H. Breuer. 1971. Are
your Charolais getting the minerals they need? Charolais Banner,
p. 104-109.
16. Underwood, E. J. 1971. Trace Elements in Human and Animal Nutri-
tion, 3rd ed. Academic Press, New York & London.
17. Zook, B. C., J. L. Carpenter, and R. M. Roberts. 1972. Lead poi-
soning in dogs: occurrence, source, clinical pathology, and electro-
encephalography. Am. J. Vet. Res. 33(5):891-902.
18. Zook, B. C., L. Kopito, J. L. Carpenter, D. V. Cramer, and H.
Schwachman. 1972. Lead poisoning in dogs: analysis of blood,
urine, hair, and liver for lead. Am. J. Vet. Res. 33(5):903-909.
43
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44
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ADVERSE HEALTH EFFECTS OF TRACE MATERIALS
IN THE ENVIRONMENT
G. J. Love
Abstract
Trace metals produced varied systemic effects, related to the total
quantities absorbed from water, food and air. These effects cover a
wide range of biologic responses ranging from increased pollutant bur-
den to death.
Because ambient air concentrations of most trace materials are low,
most effects are produced by Ibhg^term continuous or intermittent ex-
posure. Hence, epidemiological studies would be difficult to undertake.
Studies of pollutant burdens provide an alternative method that is use-
ful for monitoring environmental exposure, for indicating biologic
response, for obtaining information relative to the establishment of
environmental standards, for reference points for research, and for
safeguarding recycling technology. The application of these techniques
is demonstrated in the studies of lead, mercury, beryllium, and asbestos
that have been of recent concern to the Environmental Protection Agency.
Introduction
The human organism is exposed every day to a variety of stresses which
in toto exert considerable effect on its well-being. Some of these,
such as temperature, humidity, or pathogenic agents, we accept as being
natural; and even though we try to control, artificially, the effects
of these factors, we give little thought to the idea that they might be
eliminated.
The realization that some of the chemical substances to which we are
exposed may produce significant stress on the human body has developed
in relatively recent times. We now know, however, that a number of
illnesses or conditions formerly thought to be restricted to industrial
situations might be occurring in nonoccupational situations as well.
These stresses we do think of as lending themselves to elimination and
the fact that the illnesses could occur is sufficient incrimination to
produce the pressure needed for enactment of legislation designed to
protect the general public against the possibilities.
Environmental pollutants such as heavy metals or trace materials are
more difficult to study than are the major gaseous pollutants; it is
more difficult to develop control strategies against them because effects
can vary so widely and total exposure is almost impossible to ascertain.
Whereas the major gaseous pollutants, with the exception of CO, produce
effects at the point of contact, effects of trace metal pollutants are
caused by the total quantities of the material ingested and produce
systemic effects over a wide biologic spectrum (Figure 1). These effects
can be death when exposure is at extremely high levels, or overt disease
at somewhat less exposure. At the other end of the spectrum, the effect
45
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is restricted to an increased body burden. This is the initial response
to exposure. Between the increased pollutant burdens and the overt
disease is a broad area of altered physiologic activity, first of no
significance, but at higher or continued levels of exposure, these
alterations may become greatly significant.
/TV
Morbidity
Adverse
Health
Effects
Pathophys iolog ic
Changes
Physiologic Changes of
Uncertain Significance
Pollutant Burdens
^ Proportion of Population Affected——^
Figure 1. Spectrum of biological response to pollutant exposure.
Since ambient levels of trace metals generally are relative low and
overt effects usually are produced by long-term continuous or intermit-
tent exposure, epidemiologic studies are more difficult than usual to
undertake, and they are very expensive. Primarily for these reasons,
little information is available about the effects of chronic exposure
to ambient levels of the pollutants. Most of the knowledge we have
comes from occupational studies. On the other hand, the number of
materials about which information is needed is growing daily, since
several thousand new chemicals are developed each year and commercial
uses are found for several hundred of these. The alternative to study-
ing the mortality and morbidity that might be observed in the relatively
small number of individuals indicated by the top of the response spec-
trum is to study the pollutant burdens indicated by the bottom of the
biologic response spectrum which can be observed in many people.
By definition, a tissue carries a pollutant burden whenever it contains
a residue greater than that needed for optimal growth and development;
but in practice, measurement of pollutant burden means determining the
total quantity present. Everyone has multiple pollutant burdens and
46
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these can serve as monitors of environmental exposure, as indicators of
biological response, as inputs into environmental standards, as channel
markers for research, and as safeguards for recycling technology.
Pollutant Burdens as Monitors of Exposure
Human tissues selectively absorb and store particular trace materials.
Some tissue, such as hair, may actually record pollutant exposures for
different time intervals. To utilize pollutant burden data for this
purpose, however, it is necessary that the complexities of exposure and
metabolism be understood. For example, our intake of cadmium involves
air, water, food and tobacco smoke. All pollutant absorption is a
function of exposure route, physical form and chemical composition.
Lead fume is rapidly and almost completely absorbed from the lung, and
lead bound to respirable particulates is largely absorbed. Conversely,
lead bound to large suspended particulates fails to penetrate deeply
into the respiratory tract and is removed by the cilia of the tracheal-
bronchial tree to the throat and then swallowed. Absorption from the
gastrointestinal tract is relatively limited. In addition, organic lead
compounds are much more readily absorbed and are more toxic than are
inorganic lead compounds. And finally, the distribution, storage and
excretion kinetics generally are even more complicated than those of
exposure and absorption. Biological half lives of pollutants differ
greatly; for mercury it is 80 days, for lead 10 years.
Different tissues selectively concentrate different pollutant residues.
Tissues with high lipid content like fat and brain serve as depots for
Kr85, alkyl mercury, chlorinated hydrocarbon pesticide, and polychlor-
inated biphenyl plasticizer residues. Liver and kidney retain most of
the body cadmium, while lead, selenium and strontium concentrate in
bones and teeth. Similarly, lung retains some pollutants including
asbestos. However, when sampling living populations the epidemiologist
usually must focus on more available specimens, which may be limited to
hair, blood and excreta.
On occasion, human tissues preserved for various purposes have furnished
insights into current pollution problems. Environmentalists have util-
ized museum specimens to gain further insight into pesticide, plasticizer
and trace element pollution problems. There is a pressing need for human
tissue banks to build an environmental flashback capability and we in the
Environmental Protection Agency (EPA) are initiating such an effort dur-
ing the current fiscal year to provide rapid information when needed
relative to the several thousand metallic and synthetic compounds which
potentially involve human exposures and human pollutant burdens. Not
many years ago, infectious disease investigators encountered similar
problems with unknown agents and set up a network of sera banks which
have permitted them to rapidly assess the relationship of newly isolated
microbes to older isolates, to disease syndromes, and to the factors of
age, sex, race, residence and time. The tissue bank will provide a
similar service for studies of nonbiologic etiologies. A coordinated
tissue bank program perhaps must overcome obstacles inherent to standard
tissue preservation; but freezing, lyophilization, and irradiation seem
to be the methods of choice, with special care being devoted to containers.
47
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Less dramatic but more useful tissue banks would involve easily preserved
tissues like hair, desiduous teeth, and nail clippings collected from
living populations whose environmental exposures are concomltantly meas-
ured.
Pollutant Burdens as .Indicators of Biological Response
Human pollutant burdens can be related to the biological responses
previously mentioned. These studies attempt to relate to response to
tissue levels in responding members.
Studies in populations, however, must be interpreted very carefully.
For instance, a given pollutant burden might represent a minor risk for
an industrial population of medically prescreened adults and a major
risk for susceptible groups in the general population. Susceptible
groups include the pregnant mother and her fetus, infants and children,
the elderly, and patients with chronic disease or other deficiencies.
Age, sex or place of residence also may affect the extent of pollutant
burden.
Pollutant Burden Input into Environmental Standards
One method of providing protection against environmental pollutants is
the promulgation and enforcement of ambient air or emissions standards.
Standards for pollutants characterized by direct exposure from a single
environmental medium are set by considering control technology and the
associations between pollutant levels and adverse effects and then em-
ploying a safety factor. Sets of standards for pollutants impinging
upon man through multiple environmental media are much more dificult to
derive. One input into such standards will be the pollutant burden of
populations at greatest risk. For these pollutants, routine monitoring
of population burdens can be at least as important as environmental
monitoring. Population burdens may also delineate a priority order for
standards development.
Also, critical evaluation of each standard established is necessary;
and monitoring changes in human pollutant burdens is one way to deter-
mine whether standards actually are achieving environmental quality
goals. Increasing pollutant burdens would warn that environmental con-
trols are inadequate. Should population burdens approach levels associ-
ated with clinical toxicity, environmental standards would have failed
and emergency action would be indicated.
Pollutant Burdens as Channel Markers for Research
Pollutant burden patterns can serve as channel markers for research,
particularly in studies of chronic diseases or investigations of terato-
genic, carcinogenic, and mutagenic hazards.
Pollutant Burdens as Safeguards for Recycling
In the past, control technology has focused upon disposal of waste
products; but in the future, much more emphasis will be placed upon
48
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recycling, particularly for limited resources. The feasibility of
recycling treated sewage water directly into municipal reservoirs, of
consuming food products in whose growth or development solid wastes
have been used, has been questioned by those who fear technology may
not sufficiently safeguard the consumer. When recycling systems are
utilized, appropriate human pollutant burdens should be monitored along
with the recycled products.
To illustrate some of the ways in which pollutant burden information or
the lack of it has created difficulties, let us consider some of the
current responsibilities of the EPA. The first is related to the need
to remove lead from gasoline. Lead is a ubiquitous substance, the
toxicity of which has been known for many years.
We have been aware, for instance, of occupational hazards or the conse-
quences of using pottery made from materials containing significant
quantities of lead, when it is not properly glazed. But when it was
decided that to control pollutants being emitted from automobiles it
probably would be necessary to remove all lead from gasoline, it became
necessary to assist with this effort by determining the extent of any
•health hazard that might be related to atmospheric lead.
Actually, most cases of clinically recognizable lead poisoning in the
United States are included in three groups: (1) workers in lead trades,
'(2) people who .consume illicitly distilled spirits which often consist
of lead-contaminated alcohol, and (3) young children living in urban
areas. There are adequate laws covering occupational exposures, and
today, problems are rare. I understand that as taxes go up, the quan-
tities of illicit liquor increase also. So the solution to that problem
should be simple. The major environmental problem, then, is concerned
with young children in urban areas. To try to determine just how much
lead pollution contributes to this problem, it is necessary to make a
number of assumptions.
The major source of lead for nonoccupationally exposed adults is the
diet. The average daily intake from food is about 300 yg, with a range
of 100 to 500 yg. Data indicate that this intake has not changed
significantly in the past thirty years. The daily intake of lead from
water has been estimated to be about 20 yg. Less is known about the
dietary intake of lead by children, but the little information available
suggests that daily intake ,in children can be significantly higher than
300 yg. :' .; ' .> s -
Only a fraction of the lead ingested in the diet is absorbed from the
gastrointestinal tract.'• (Lead balance studies in adults have shown that
the average absorption over long periods of time is 5-10% of the in-
gested dose when intake 'is not excessive. Therefore, it can be calculated
that in adults about 15-30 yg of lead are absorbed from the diet each day.
The exact proportion of dietary lead intake that is absorbed by infants
and children has not been determined, and it must be assumed to be similar,
During periods of normal intake, about 90% of the lead appears in the
feces. A small amount obviously may initially be absorbed and then
49
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excreted back into the gastrointestinal tract. Most of the remainder
of that not retained in the body can be found in the urine.
the contribution of airborne lead to the total amount absorbed each day
has not been defined precisely, but some estimates have been made.
Experiments with air containing 150 yg/m3 of lead particulate matter
with a mass median diameter of 0.25 y showed that, in adults, 36% of
the lead was deposited in the airways. It must be assumed, then, that
a similar percentage of lead would be deposited when air containing
concentrations of lead in the range of 1-10 yg/m3 was inhaled, and that
all of the lead deposited in the respiratory tract is absorbed into the
body. From these assumptions, it can be predicted that the total daily
absorption of lead from the air by a "standard man" engaged in light
activity would range from 0.8 to 63 yg, depending on where he lives and
works. The percentage of inhaled lead that is deposited in the respir-
atory tract :of infants and children has not been determined experimentally;
however, if it is assumed that the deposition is similar to adults (i.e.
about 36%) and that the deposited lead is absorbed into the body, the
amount of lead absorbed f.tom the air can be estimated.
If other simplifying assumptions are made, a dose-response curve relating
the concentration of lead in the blood to the daily absorption of lead
from all sources can be constructed. For this purpose, epidemiologic
data have been used which indicate lead concentrations in the blood of
various groups of men whose estimated exposure to atmospheric lead had
differed. The contribution of lead in the air to the daily absorption
was estimated by using the assumptions mentioned above (i.e., that
similar percentages of inhaled lead particulate matter are deposited in
the respiratory tract, regardless of the concentration of lead in the
inhaled air, and that all the lead that is deposited in the airways is
absorbed). The amount of lead that will be absorbed from inhaled air
is equal to the airborne lead concentration times the volume of air
inhaled per day (about 23 m3) times the percent of lead deposited in
the respiratory tract. For example, if a person inhales air containing
2 yg of lead per cubic meter, and a conservative 30% respiratory depo-
sition is assumed, then the lead absorption from the air can be
calculated as follows: 2 yg/m3 x 23 m^ x 30% = 13.8 yg. An individual's
total daily lead absorption can be calculated by adding daily dietary
lead absorption (about 30 yg) to the amount absorbed from air.
Elevated blood leads and thus excess body burdens are associated with
airborne .lead levels greater than 2.0 yg per cubic meter. Increased
urinary excretion of delta-aminolevulinic acid begins at blood lead
levels of about 40 yg per 100 g of whole blood. Subtle signs of clinical
lead poisoning have been associated with blood lead levels of about 50 to
80 yg per 100 g of whole blood. At the present time, there are no epi-
demiologic data which relate the lead concentration in the blood of
infants and children to their estimated exposure to atmospheric lead.
On the basis of these data, a case has been made for the control of lead
to protect the health of children in urban areas. This case argues that
levels of atmospheric lead in excess of 2 yg/m3 are accompanied by the
-following' implications:
50
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1. There is an increase in the accumulation in the body of a heavy
metal with no known biologic usefulness but of known toxicity
at moderately increased blood levels.
2. It can be shown that a substantial contribution to this body
burden may come from atmospheric lead.
3. And finally, the question is raised concerning the consequences
of an increased contribution to body burdens now found in urban
residents. If the problem is pretty well restricted to child-
ren in these areas, there must be some factors peculiar to
these, areas. The argument must then acknowledge that at best,
ambient atmospheric concentrations of lead are not directly
toxic, but they may be indirectly toxic by increasing the risk
of toxicity resulting from total intake of lead. Such indirect
effects may relate either an added increase in the body burden
of lead or to an increased risk of poisoning in young children
who ingest excessive lead from other sources.
As far as other sources are concerned, we are familiar with the problem
of lead toxicity associated with ingestion of paint chips containing
larger quantities of lead; but there is another source that might be
less significant yet should not be overlooked. This is dustfall in
urban areas.
Dustfall in metropolitan areas contains a high proportion of lead,
ranging from 1636 yg/g dust in residential areas to 2413 yg/g dust in
commercial areas. Values up to 3397 yg/g dust have been collected close
to heavily traveled roadways. These quantities may appear to be more
significant when it is remembered that 1 yg/g is the equivalent of 1 ppm.
These are the levels of lead in the dust found in city streets where most
urban children play. So, while ingestion of leaded paint clearly is the
principal cause of lead poisoning among children, it probably does not
account for the approximately 25% of children who in mass screening
programs in inner city areas did not appear to have clinical lead poison-
ing but had blood lead levels exceeding 40 yg Pb per 100 g blood.
According to a recent NAS report, dust may well account, in large part,
for the higher mean blood lead content in urban children and the rather
large fraction of these children whose blood lead content falls in the
range of 40-60 yg per 100 g of whole blood, thereby bringing them into
the range in which increased urinary excretion of ALA may be observed.
Based on the evidence presented, it was concluded that airborne lead
levels exceeding 2 yg/m3 averaged over a period of three months or longer
are associated with a sufficient risk of adverse physiologic effects to
constitute endangerment to the public health of sensitive segments of our
population. Since airborne lead levels in many major urban areas current-
ly range from 1-5 yg/m3, and since motor vehicles are the predominant
source of airborne lead in these areas, attainment of the 2.0 yg/m level
would require a 60-65% reduction in lead emissions from motor vehicles.
EPA also has the responsibilities for designating hazardous air pollu-
tants whenever it is believed that emissions from specific sources may
endanger human health. Such designation requires the establishment of
51
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emission standards and designation of atmospheric levels at which the
federal government will take emergency action. Three substances have
been designated to date: asbestos, beryllium, and mercury; and the
pollutant burden concept was prominent in the selection of recommenda-
tions for permissible ambient exposures or the significant harm levels.
Asbestos. The ability of asbestos to produce lung disease in the form
of asbestosis has been known for many years. More recently, it has
become apparent that asbestos exposure is associated also with the
development of pleural plaques, cancer of the lung and digestive tract,
and mesothelioma, an uncommon form of cancer. Both types of illness
have been associated with the inhalation of asbestos fibers. Sufficient
data have been collected to define what are believed to be reasonably
accurate dose-response relationships for asbestosis. One consistent
epidemiologic feature of the illness is that it develops only after many
years of continuous heavy exposure and is not reported outside industry.
The second type of illness has been shown much more recently to be
associated with asbestos exposure and the epidemiologic relationships
are not consistent. Cancer, especially mesothelioma, has been reported
following exposures ranging from a few months to a few years and has
been reported in persons living near asbestos mills as well as in
factory workers.
The lack of dose-response relationships suggest that asbestos workers
may not differ in their susceptibility to these malignancies from other
segments of the population of the same age. The more susceptible
individuals, even among the asbestos workers, may develop the illness
as a result of short exposures to significant quantities of asbestos
fibers or maybe under unusual exposure conditions not presently under-
stood.
Present methods of sampling, identifying, and measuring airborne asbestos
are not entirely satisfactory, especially if one is dealing with the low
fiber concentrations that have been demonstrated in ambient air. The
demonstration of ferrunginous bodies and the positive identification of
chrysotile asbestos fibers in lung specimens from persons with no occu-
pational contact with asbestos indicates that these persons have inhaled
and retained asbestos. Since there were no dose-response data available,
EPA declined to indicate a "number" emission standard but is dependent
for control on the maximum elimination of emissions. This, however, did
not eliminate the requirement for indicating the significant harm level.
This was derived in the following manner. A standard, proposed for
occupational exposure to airborne asbestos, is a maximum of 2.0 asbestos
fibers per cubic centimeter (cc) of air based on a count of fibers
greater than 5 micrometers (>5 ym) in length, determined as a time-
weighted average (TWA) exposure for an 8-hour work day, and no peak
concentration to exceed 10.0 fibers/cc >5 ym as determined by a minimum
sampling time of fifteen minutes. If the TWA exposure for an 8-hour day
is converted to a TWA exposure for a 24-hour day, this would permit 0.6
fibers/cc >5 ym for 24 hours. A worker does not work every day in the
year, and if it is assumed that he works approximately two-thirds of the
days, 0.4 fibers/cc >5 ym is the TWA exposure for a 30-day exposure
period.
52
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Applying a safety factor of 2 to the above, the recommended imminent
endangerment to health levels for asbestos above natural background
levels for the general population are as .follows:
1.0 fibers/cc >5 ym TWA exposure for 8 hours
0.3 fibers/cc >5 pm TWA exposure for 24 hours
0.2 fibers/cc >5 pro TWA exposure for 30 days
Peak exposure to asbestos shall not exceed 5.0 fibers/cc >5 pm as
determined by a minimum sampling time of fifteen minutes.
Beryllium. When beryllium or its compounds is inhaled by humans or
animals, it can cause various systemic diseases with pulmonary damage
being of major concern. An acute chemical pneumonitis has been produced
by inhalation of virtually all beryllium compounds. The total response
seems to be dependent upon the degree, duration and type of exposure.
Rapidly fatal cases have resulted from exposure to large concentrations
of soluble salts in beryllium-processing industrial plants.
Most commonly, however, a chronic illness develops that is insidious
in nature, developing as a dry cough and progressing to substernal
discomfort and pain, general weakness and fatigue, and loss of weight.
Attempts to correlate this chronic effect with time and duration of
exposure have been unsuccessful. The delay in onset of manifestations
can vary from months to many years. The illness is of long duration
with a high mortality rate. Cases have occurred in persons exposed to
beryllium in many forms in a wide variety of occupations and in persons
not connected with the processing of beryllium but residing in the
neighborhood of beryllium plants. The evidence also indicates that at
least one member of a household of a workman employed in a beryllium
plant contracted the disease from exposure to dust carried home on
clothing.
Studies of chronic beryllium disease have demonstrated no simple dose-
response relationships. Cases of chronic disease have occurred following
exposures to low concentrations of a beryllium compound while no disease
was produced at higher levels of exposure.
Thus, beryllium has been shown conclusively to be a hazardous substance
even when esposure is to relatively low levels. Beryllium is unique in
that there are three standards which stipulate, for different conditions,
the permissible concentrations of beryllium and beryllium compounds in
the air. One standard, designed to prevent acute occupational beryllium
disease, sets a limit for peak exposures at 25 pg Bd/m3 for not to
exceed 30 minutes. A second standard, designed to prevent chronic
occupational beryllium disease, provides that in-plant atmospheric
concentrations of beryllium should not exceed 2 pg/m3 as an average over
an 8-hour day. The third was proposed to prevent non-occupational
chronic beryllium disease in communities around beryllium extracting
and processing plants. This stipulates that the average monthly concen-
tration of beryllium at the breathing zone level in the communities
should not exceed 0.01 pg/m3. Assiduous adherence to these standards
apparently prevents new cases of beryllium disease.
53
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Acute non-occupational beryllium disease has not been reported in the
United States in the neighborhood of beryllium plants; therefore, there
is no need to indicate a maximum or peak exposure level to prevent acute
disease as long as the required lower level of exposure designed to pre-
vent chronic disease is maintained. The non-occupational monthly mean
limit of 0.01 yg/m3 was based upon the report with 11 persons with non-
occupational chronic beryllium disease in the area surrounding a
beryllium-in-air concentration which produced the disease was greater
than 0.01 yg/m3 but probably less than 0.10 yg/m3. The 0.01 yg/m3 value
was therefore established as the out-plant limit.
Recognizing that the scientific back-up of these levels is weak, it was
believed to be more prudent to recommend that the level designated to
represent imminent and substantial endangerment to health and therefore
the level never to be reached in the ambient air should be 3 times the
proposed out-plant limit rather than 2 times this limit, or an average
monthly concentration of 0.03 yg beryllium/m3 at the breathing zone
level. This assumes that the ill subjects used as the basis for the
standard probably represented more susceptible individuals exposed to
levels of beryllium in excess of 0.01 yg/m3 and that chronic illness
can result from exposures of little more than one month duration.
To protect non-occupationally exposed subjects in special situations
such as observers at a rocket launch or residing in the vicinity of a
test site, limits of 2.5 yg beryllium/30 minutes were selected to
represent the absolute maximum permissible exposure. (2.5 yg Be/30 min.
= .05 yg/day if for the remaining 23.5 hours exposure was zero.) This
is one-tenth of the 30 minute maximum concentration permitted in industry
and is selected arbitrarily as a level to protect the general population
against acute effects. A 3-hour maximum permissible exposure of a mean
level of 0.4 yg Be/m3 should be imposed in addition to the 30 minute
maximum.
The 30-day significant harm level of 0.03 yg/m3 permits considerably
less inhalation of beryllium than does the industrial TLV of 2 yg/m3 for
a 40-hour week which corresponds quantitatively to approximately 0.5
yg/m3 continuous exposure. However, possible differences between the
effects produced by continuous exposure and those produced by intermit-
tent industrial exposure are not understood, and evidence indicates that
sensitive individuals can develop chronic beryllium disease at continuous
exposure levels not greatly in excess of 0.01 yg/m3.
Mercury. Inhalation of air contaminated with mercury vapor or certain
mercury compounds may produce intoxication or poisoning resulting from
the absorption of toxic amounts by tissue in the respiratory tract.
Furthermore, inhalation of mercury vapors or mercury compounds may be
more detrimental to the body than is ingestion of these materials. Data
suggest that absorption through the respiratory tract leads to a higher
rate of accumulation of mercury in the brain than results from other
routes of absorption. Once mercury passes the blood-brain barrier, it
becomes more strongly bound in the brain than in any other organ of the
body. The organic mercury compounds in general are more toxic than
elemental mercury or its inorganic compounds.
54
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Health effects related to absorption of mercury range from pneumonitis,
gastrointestinal and central nervous manifestations in acute instances
to a particular form of anxiety neurosis, erethism, the most character-
istic result of toxic chronic exposure. No information is available
on the minimum, concentrations of mercury that will produce chronic
poisoning.
i
Recently, considerable publicity has been given to the problem of
mercury pollution in water. It has been learned that as a result of
bacterial action, inorganic mercury can be converted to the more toxic
organic forms and as such may be stored in biologic tissues. These
concentrations can become greater and more significant as they move
through a food chain until eventually some member of the chain can in-
gest a toxic dose. This bio-accumulation in food chains was documented
first by the investigations of Minamata disease in Japan and subsequent-
ly in other parts of the world. How much atmospheric pollution with
mercury may indirectly contribute to the levels of water pollution is
unknown.
A safe level of atmospheric pollution with methylmercury or mercury
vapor that could be established as a reasonable ambient air quality
standard is 1 yg/m3. This level is derived from the following data:
1. A daily intake of 300 yg Hg as methylmercury would be expected
to produce at equilibrium a blood Hg level of 0.2 yg/g whole
blood. This is the blood Hg level at which the onset of
symptoms would be expected in the most sensitive individuals.
2. One-tenth of 300 or 30 yg Hg is selected arbitrarily as the
maximum daily intake of Hg that should be permitted in the
general population, thus providing a comfortable margin of
safety.
3. The permissible intake of 30 yg Hg per day may be obtained
from water,ifood, and inhaling 15-20 m3 of air. At an air
pollution level of 1 yg/m3 15-20 yg Hg would be inhaled each
day, leaving approximately one-third of the total or a maximum
of 10-15 yg to be ingested in food and water.
4. Although there might be some argument about the accuracy of
figures for the Hg content of food and water to arrive at the
estimates for potential total intake, there probably is suf-
ficient safety included in the recommended level to allow for
a 100% error.
On the basis of these same data, it is recommended that the "significant
harm" level of air pollution be established at 10 yg Hg/m for the
following reasons:
1. If 300 yg daily intake can produce symptoms in sensitive
individuals, this level of intake should not be permitted for
even one day because no assumptions can be made about prior
exposure for any individual.
2. In an area in which the atmospheric concentration of Hg is
increased significantly, the quantities of Hg in food and water
55
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might also be increased. Perhaps this would not be expected to
occur immediately, but the possibility cannot be ruled out.
3. Consequently, if the "significant harm" level of Hg is cpn^
sidered to be a total daily intake from all sources of 300 yg,
the maximum permissible contribution from air can be determined
in the same manner used to estimate a safe air level.
4. This determination would indicate that a maximum intake of Hg
from food and water might be expected to remain consistent at
approximately one-third of the total intake of 100 yg at a
time when total intake from air would be 100 yg Hg. If the
total quantity of air inhaled each day is accepted as 20 m^,
this establishes the potential imminent endangerment level °f
Hg air pollution at 10 yg/m3 24-hour mean.
5. This recommendation assumes that differences in toxicities of
mercury vapor and methylmercury are not excessively great at
lower levels of exposure and, therefore, the figure was derived
as if these toxicities are equal. If subsequent research
demonstrates that this assumption resulted in an overly-?
stringent standard, the level can be revised.
It is recognized that the 24-hour mean atmospheric mercury levels
recommended here to be the level of potential significant harm within a
population is the same numerically as the 8-hour industrial TLV for
methylmercury. However, for the purpose of this recommendation, methyl-
mercury and elemental mercury have been considered to be equivalent,
when in reality there is little likelihood that atmospheric mercury will
include significant quantities of methylmercury. It was believed that:
the assumption is necessary to permit applicable and timely measurements
of atmospheric mercury. In industry, the TLV for elemental mercury ^s
now 100 yg/m3, but it is planned that this will be reduced to 50 yg/m3.
The recommended significant harm level is considerably higher than the
levels measured even in the worst situations within the United States.
It is designed, however, to prevent for a single day the level of
exposure that on a continuous daily basis is indicated to result at
equilibrium in a blood mercury level of 0.2 yg/g blood if one-third of
the total daily intake is obtained from food and water. A level of 0.2
yg/g blood is associated with the onset of symptoms in the most sensitive
individuals.
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ENVIRONMENTAL CHEMICALS AND CARCINOGENESIS
Hans L. Falk
The evaluation of carcinogenic hazards for man on exposure to environ-
mental chemicals has been of very grave concern to agencies of the
government, to investigators at universities and in industry, and through
newspaper reports to the general public. The question whether a human
cancer hazard exists has been answered to the best of everybody's
ability in the positive or negative, depending on oners point of view.
It has become painfully clear that relevant data on carcinogenic hazards
for man have been sparse or altogether absent, and conclusions have had
to be based on animal data. These studies even under the most careful
planning and with the greatest precision have obvious limitations in
the extrapolation of their results to man. In this paper, I will try
to illuminate what is known and what is only surmised, taking DDT as an
example, to explore the questions that have to be answered for an accep-
table conclusion on carcinogenic hazards.
The simplest task is the evaluation of existing laboratory data for
scientific adequacy of design and execution. It is here that science
has its well-established rules, and conclusions can be accepted by all
who utilize the scientific method. Nonetheless, even in laboratory
experimentation and interpretation of results may be some room for
heated discussion and disagreement. These are based on incomplete
knowledge that is always encountered when a study is initiated and before
hindsight prepared the way to easy criticism. However, many pitfalls
have been recognized and remedied.
In testing a compound for its carcinogenic activity, it is often impos-
sible to know its purity or the nature and amounts of impurities present
in the available commercial product. It is, however, necessary to be
aware of potential impurities but not to rely on the absolutely pure
chemical for this first bioassay as one may otherwise miss hazardous
substances which may only be present as impurities. The objection has
been raised that one can never come to any conclusion if one is dealing
with commercial products which with time may be altered in composition.
This is a justified criticism and may lead to additional studies being
carried out involving the pure components in order to get more informa-
tion towards understanding this hazard.
Once we have reached acceptance of the chemical of choice and have
obtained adequate information on its chemical and physical properties
and impurities, it will still be necessary to concern oneself with the
adequacy of the biological parameters of the study to be undertaken.
Many of these are rapid tests and give essential information which serve
as basis for decision for the long-term study to follow. The degree of
absorption of the chemical from the environment needs to be established,
be that through the lung, from the gastrointestinal tract, or through
the skin and such studies must be followed up by others on retention and
distribution throughout the body, together with rates of elimination
which may depend on the metabolism of the compound. This information
may be crucial in alerting us whether we have a hazardous substance in
hand or whether the situation may never become serious.
57
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For many chemicals, we have adequate information on purity and on the
nature and extent of the impurities which are encountered. We are well
informed of the stability and degradation of the compound in the envi-
ronment; and we may know about its absorption, retention, storage,
metabolism, and elimination from experimental animals. We can, there-
fore, answer adequately the important questions of whether the compound
will be around long enough to be considered a potential hazard, or
whether it can be destroyed and eliminated at a fast enough rate to be
considered harmless. In the case of DDT, we know that its degradation
is slow and, under certain conditions, may not take place at all, and
that it can be absorbed and metabolized but that the process of metab-
olism in many species does not necessarily lead to a non-toxic compound.
Although one of the major metabolites seems to be harmless for insects,
in mammals DDE is quite toxic and possibly carcinogenic.
With these data in hand, one may be considered adequately equipped to
undertake long range toxicological studies to determine if carcinogenic
risk exists for future extrapolation to man. One may not as yet have
adequate information on absorption, retention, and metabolism in humans
until a spectrum of responses from different people has also been
obtained. In the case of DDT, this kind of information is available;
and for mammalian species, including man, qualitative differences in
the handling of the chemical do not seem to exist.
Carcinogenic studies which have been carried out in the past have always
involved a limited number of animals by necessity; and in order to ob-
tain adequate information on tumor incidence, the dose to be administered
had to be increased considerably, preferentially to a level where the
chemical would not produce lethality or morbidity for an extended period
of time. Such tolerance of the dose of test chemical is monitored by
acceptable weight gain and lack of mortality for months while on the
test chemical.
Although we may seem satisfied in general about the method of administra-
tion of the chemical, which is often oral administration, there are other
parameters which present the basis for disagreement. These deal with the
quality of the animal itself. It should be recognized that much is un-
known about the test animal with regard to its weaknesses and suscepti-
bilities. Many times, the choice of a particularly susceptible strain of
animal is counter-indicated, while a particularly resistant strain may be
recommended. This argument is often solved by recommending the choice of
non-inbred animals as this would eliminate this impass, whether the
resistant or the susceptible strain is the most desirable for this study.
The choice of the correct strain or species will depend on the specific
condition that the experiment is to clarify.
With regard to quality of the diet, its stability and its contamination
by pesticides, protection of animals against infection by viruses or
bacteria or even deodorants and disinfectants that may be used in the
laboratory and which may cause enzyme induction, thus changing the
handling of the test compounds, experiments must be controlled. The
results of these studies then will be utilized to determine whether a
carcinogenic hazard may exist for man. In the case of DDT, it must be
concluded that for mice, at least, a carcinogenic hazard does exist.
-------
The problems we encounter in extrapolation from one species to another
are based not only on differences in susceptibility for which we often
have no information, but also on the comparability of the mode of
administration and the dosing. These findings can be utilized to
argue in several directions and frequently it is the decision founded
more on the emotional rather than the scientific basis that prevails.
As there are few data on environmental chemicals causing cancer in man
but quite a collection of experimental data concerning conditions of
exposure that have resulted in the production of cancer in animals,
these facts can be reviewed to see how closely they correspond to the
human exposure and what early signs of a parallel toxicity can be
detected which might give us spme confidence that parallel events have
occurred. , '
For pesticides at very high dose levels, responses can be observed on
the neurologic basis which may be considered similar for many species.
At a lower dose level, no toxicity may be observed in any species, but
a level of intake may be reached when a completely different type of
toxicity is seen. It is referred to as the level of enzyme induction.
This effect, generally considered as advantageous and helping in the
detoxification of foreign chemicals, has been detected in humans as well
as experimental animal species and shows considerable similarity in all
species. It has been observed in the liver, the gastrointestinal tract,
the lung, the skin, and other organs. With certain chemicals, this
beneficial effect of facilitating detoxification backfires, and metabo^
lism yields a more toxic product. It may also cause the rapid destruc-
tion of a compound needed for its biochemical activity, as happens in
the case of certain drugs or steroid hormones.
It is generally assumed that on the cellular level, processes of detox-
ification may be parallel in specific organs of many species, but it
should not be implied that these similarities are quantitative. Often,
the same enzyme systems have been detected and the same metabolites have
been identified, but there is no certainty that under all circumstances,
the fate of the foreign chemical will be the same and that in the human,
metabolism will lead to quantitatively similar end products. We know
from experience with drugs and foreign chemicals that we do not obtain
the same level of detoxification or the same rate of excretion and thus
the same degree of toxicity in otherwise quite comparable species or
individuals. Thus, although we have acceptable data on the carcino-
genicity of various environmental chemicals, we must exercise care in
interpreting the results by including well-documented variations in
human metabolism and specific variations in response in this delibera-
tion. The median human response does not coyer enough of the total
population at risk.
As pesticides have been of particular interest to many investigators
during the last ten years, data on carcinogenicity of these compounds
will be quickly reviewed. Such a review must be based on several
factors: First, the persistence of the chemical will determine whether
only the manufacturing and dispensing worker will be at risk or if the
ultimate consumer may also be affected, even though he may not be aware
of any exposure.
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Since no epidemiologic findings suggesting a carcinogenic hazard have
been associated with workers handling carbamate or organophosphate
insecticides and since they are comparatively unstable so that they dp
not tend to persist for a long period of time, these compounds may not
present a carcinogenic hazard for the general population on long range
exposure to products that have in the past been breated with these
insecticides. For the stable or poorly degraded insecticides, human
epidemiologic data which would suggest a carcinogenic hazard are also
unavailable; but because of their environmental persistence, animal
experiments have been carried out; and for this group of compounds,
positive data were obtained. This applies to some extent to most of
the chlorinated hydrocarbon insecticides tested where on chronic feeding
of high dose levels, the liver gave rise to hepatomas. Adequate dose-'
response data have not been obtained in most cases; but in each study,
the level tested was the highest level that was tolerated over an
extended period of time without weight loss. A number of pesticides
have been singled out as presenting potential hazard by the realization
that with increased usage, more pesticide could be stored in tissues of
animals and man and a level could be reached which may be critical for
the production of tumors. In the Report of the Secretary's Commission
on Pesticides and Their Relationship to Environmental Health, pesticides
have been subdivided into groups representing those that should be kept
out of foods, those that should be further investigated, and those that
apparently represent no hazards. They are listed in Tables 1 •<• 5.
TABLE 1
Compounds judged positive for tumor induction on the basis of
tests conducted adequately in one or more species, the
results being significant at the 0.01 level.
Registered for use Registered, but not for
on food crops use on food crops
Aldrin Amitrole
Aramite Avadex (Diallate)
Chlorobenzilate Bix (2-chloroethyl) ether
p,p'-DDT N-(2 hydroxyethyl)-hydrazine
Dieldrin PCNB
Mirex
Strobane
Heptachlor1
1 Assigned to this group because a metabolic product, hep-*-
tachlor epoxide, was judged positive for tumor induction,
results being significant at the 0.01 level.
60
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TABLE 2
Compounds yielding an increased tumor incidence significant
at the 0.01 level but considered less tumorigenic than the
mean of a group of positive controls. These compounds
have first priority for additional testing.
Registered for use Registered, but not for
on food crops : use on food crops
p,p'-DDD Azobenzene
Monuron CCC
Perthane Chloranil
Piperonyl butoxide Cyanamide
Piperonyl sulfoxide Vancide BL
. . , Zectran
TABLE 3
Compounds yielding an increased tumor incidence significant
at the 0,02 level. Similarly, they were concluded to be
less tumorigenic than the mean of the same group of
positive controls. These compounds have second
priority for additional testing.
Registered for use Registered, but not for
on food crops use on food crops
Biphenyl Genite-R99
C^ptan IPC (program)
2,6-Dichloro~4-nitroanilinel
Gibberellic acid
2-mercaptobenzothiazole
Ovejc (Chlorofenson)
1 Active ingredient in the formulation sold as Botran.
61
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TABLE 4
Compounds yielding an increased tumor incidence in comparison
with the negative controls but the level of significance was
less than 0.02, possibly because too few animals were
observed. These compounds have third priority for
additional testing.
Registered for use Registered, but not for
on food crops . use on food crops
a-(2,4-Dichlorophenoxy) 1-Naphthalene acetamide
propionic acid 2-(2,4,5-Trichlorophenoxy)
2-(2,4-DP) propionic acid
2,4-D Isopropyl ester
n-Propyl Isome
Pyrethrin
Zineb .
When reviewing the groups of compounds in each class, it is apparent that
not all members of a group are mentioned, suggesting that there is no
close structural correlation between carcinogenicity and chemical struc-
ture. This may be due to differences in toxicity so that different dose
levels had to be administered, lack of testing of the compound so that
data are not available, change in experimental design, species, strain,
or length of exposure or observation which have to be taken int;o consid-
eration if such a comparison is to be attempted.
The data that were collected in one large scale study were not meant to
be the ultimate test before extrapolations would be attempted but were
designed to be the first preliminary suggestions of hazards which must
be studied in more detail and in different laboratories before cpnclu"
sions can be drawn about legislative action to be contemplated. Only
because a hazard to man's environment was demonstrated, actions were
initiated on some of these pesticides before adequate information pn
carcinogenicity was available. In the case of DDT, additional experi-r
ments have been carried out which confirmed the earlier observations and
thus justify action already taken to curtail the use of this compound.
With regard to other pesticides which have proven to be tumorigenic to
test animals, additional experiments are needed and following the Report
of the Secretary's Commission on Pesticides' recommendations, are, I am
sure, being carried out at this time.
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; TABLE 5
Compounds which were tested appropriately in one species only and judged
not positive in that species. However, current guidelines for testing
required negativity in two species. These compounds have fourth
priority for additional testing.
Registered for use
on food crops
Registered, but not for
use on food crops
Atrazine
2,4~D
2,4-rD Butyl ester
2,4-D Isooctyl ester
Dehydroacetic acid
Dichlone
Diuron
Dodine
Orthophenylphenol
Endosulfan
Ferbam
Folpet
Glyodin
Maleic hydrazide
Maneb
Methoxychlor
Methyl Zimate (Ziram)
Nabam
Phenothiazine
Planofix: N.A.A.
Propazine
Simazine
Tetradifon
Thiuram (Thiram)
Tillam-6-E
ANTU
Cacodylic acid
Copper 8-Hydroxyquinoline
Dicryl
Diphenatrile
Dpwcide^?1
Hercules 7531 (Norea)
Isolan
Karathane
Pma; Phenylmercuric acetate
2-Sec.-butyl-4, 6-dinitrophenol
2,4,5-rT
1 While Dowcide-7 is registered for nonfood uses, its use in food con<-
tainers and packaging materials is permitted under registration.
Wooden fruit (berry) boxes may contain up to 50 ppm.
63
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64
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CHEMICAL INTERACTIONS
Frederick W. Oehme
The subject, "Chemical Interactions," is one that has only recently
attracted attention amongst health scientists. However, the importance
of chemical interactions far exceeds the limited emphasis given to it
and the even smaller body of knowledge available about this biological-
interchemical syndrome.
Most health and environmental scientists are accustomed to dealing with
individual foreign chemicals and the effect they might have on any given
biological system. We are trained to recognize the potential health haz-
ard, clinical signs and lesions, and treatment and control recommendations
for specific intoxications, such as lead poisoning, organic-phosphate
poisoning, or nitrate toxictty. Few of us, however, recognize the multi-
ple problems that may occur if two 'or more foreign chemicals are present
and affecting the body systems at one time. The frequency with which
combination drug therapy is employed in human and animal medicine and
the wide variations of environmental pollutants to which man and animal
are continually exposed give ample opportunity for multiple biological-
chemical reactions and interactions to occur. Indeed, such adverse
effects have been occurring with increasing frequency, and the widespread
availability and use of such chemicals makes consideration of their
health hazard of importance.
The purpose of this paper is to review the problem of chemical inter-
actions by discussing the physiological and chemical factors determining
how toxic agents exert their effect, suggesting proposed mechanisms for
toxic responses due to chemical interactions, and documenting implications
of such responses and suggested means for health scientists to become
more aware of and combat this growing diagnostic and therapeutic problem,
Factors Affecting Toxicity
Even the beginning scientist is aware of the normal distribution curve
and the fact that certain individuals in a population may demonstrate
greater or lesser than normal responses to given chemicals; however, t:he
vast majority of a given population will demonstrate a response closely
grouped around the mean for a given set of circumstances. These circum-
stances—those that limit variability in response—^-are themselves subject
to variation and with fluctuation in circumstances will result in in-
creased or decreased toxicologic effects.
The commonly cited factors affecting toxicity are listed in Table 1. The
dose or amount of toxin received is the single most important variable;
but practical circumstances and the increasing production of new foreign
chemicals makes all the factors significant. The toxin's physical and
chemical properties determine whether significant amounts will be ab-
sorbed. The route of exposure affects absorption and the rapidity of
onset of action. Absorption of the toxin is largely determined by its
lipid solubility, but once absorbed, the biotransformation of the chemi-
cal is a vitally important process by which primarily the liver detoxifies
65
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the material. Distribution throughout the body, metabolism by enzymes,
possible .accumulation in body tissues, and the ease or lack of elimina-
tion from the body are all additional equally important variables. Of
the factors relating to the animals involved, species differences are
most important. Anatomical and physiological differences are obvious,
but most :critical are the variations in enzyme levels and the biological
capacity for detoxification of foreign chemicals. Size, age, and sex
of the exposed animals are also important variables, with the very young
and old being more sensitive than the healthy mature individual. Females
of the species are usually more susceptible to intoxication than males.
Animals in poor health or with pre-existing liver or kidney disorders are
more adversely affected by foreign chemicals than are individuals in full
health.
TABLE 1
Factors Affecting Toxicity
1. Amount of toxin received
2. Physical and chemical properties of toxin
3. Route of exposure
4. Absorption of toxin
5. Biotransformation of toxin
a. Distribution
b. Metabolism
c. Accumulation
d. Elimination
6. Species involved
7. Size, age and sex of exposed animal
8. Health of animal
9. Individual variations
Even within groups of the same age, sex, and health, and receiving the
identical chemical via a uniform route, variations still occur in a popu-
lation. These are termed "individual variations" or idiosyncrasies.
While many of the factors producing individual variations are still
unexplained, it is felt that genetics and the inherent capacity for
detoxifying or metabolizing foreign chemicals play a large role in de-
fining these unexplained idiosyncracies.
Biological Detoxication
All individuals have mechanisms to detoxify and metabolize foreign
materials. These are normally existing systems present to various degrees
in all animals to modify the effect of an absorbed chemical. They are
outlined in Table 2.
66
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TABLE 2
Biological Detoxication
1. Physiological detoxication
a. Vomiting, diarrhea
b. Bind to protein, store in tissues
c. Excrete in breath, secretions, bile, urine
2. Biochemical detoxication
a. Enzymatic attack to increase excretion
b. Liver, kidney, intestinal mucosa
c. Make easier to detoxify further, make more water-
soluble, split or destroy
i d. Most detoxication decrease toxicity or inactivate
Foreign chemicals may be detoxified physiologically by the animal vomiting
or developing diarrhea following ingestion of the chemical. Both responses
serve to clean the digestive tract of the toxic material. Following ab-
sorption of the chemical, it may be bound to protein in the blood or
tissues. The foreign chemical may be stored in inert and inactive forms
in body fat or bone. Physiological excretion of the material from the
body may be by elimination via the breath, body secretions, bile, or
urine. Excretion by the kidney and urine is the most common means by
which the body rids itself of a foreign chemical.
The second major mechanism for detoxifying chemicals is via enzymes found
throughout the body. The purpose of enzymatic attack is to increase
excretion and thereby decrease body levels of the chemical. The liver,
kidney, and intestinal tract mucosa are especially high in detoxifying
enzymes, but all tissues in the body are capable of metabolizing foreign
chemicals to varying degrees. The goals of biochemical detoxification
are to modify the chemical so that it may be excreted more easily in the
urine, or to split or destroy the active form of the chemical so that it
is no longer capable of producing its toxic effect. While the vast
majority of detoxification steps decrease toxicity or cause inactivation
of the foreign chemical, enzymatic attack occasionally results in increased
toxicity through the production of metabolites that are more toxic than
the parent compound.
Species Differences
It was mentioned earlier that anatomical, physiological, and biochemical
differences between species of animals are major factors in determining
the effect of a foreign compound on these animals. Some anatomical and
physiological differences between species are outlined in Table 3.
Differences in digestive tract anatomy result in variations in absorption
rates in various regions of the gastrointestinal system. Animals with
relatively long digestive tracts have increased exposure time for absorp-
67
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tion. Species with large numbers of microorganisms in their digestive
tract, such as ruminents having microorganisms as an important part of
their digestive process, have a huge number of bacteria and enzymes in
the digestive tract capable of acting upon ingested chemicals. Excretory
ability varies with the degree of activity of various excretory systems.
The milking animal is more capable of excreting toxins soluble in milk
than are animals not possessing this excretory process. Not only are the
types of system available important, but the degree of activity of each
system is also critical. Animals with limited urine output would be
restricted in their capacity to excrete a toxin for which the kidney is
an important excretory route. The pH of urine varies with animal species
and affects the water solubility of the toxin and its capacity for
reabsorption by kidney tubules, versus excretion in the urine by main-
taining water solubility. Species with large amounts of body fat, such
as swine, are capable of storing toxic materials in an active form in
their tissues. Animals having limited fat would not possess this safety
factor. Dietary constituents affect the pH of urine and thereby the
degree of excretion possible via the kidneys. In addition, dietary
constituents present in the digestive tract may interfere with or enhance
the absorption of foreign chemicals. Certain species of animals are
subjected to excessive physical activities and other stresses which may
alter the metabolism of absorbed toxins. A racing animal with a high
metabolic rate will have a high rate of detoxification; individuals of
some species subjected to physical stresses will have altered liver and
kidney function, and detoxification of foreign chemicals may be decreased.
TABLE 3
Physiological Species Differences
1. Absorptivity in various regions of the digestive tract.
2. Length of the digestive tract.
3. Presence of bacteria, enzymes in digestive tract.
4. Excretory ability.
5. Methods of excretion possible.
6. Urine volume and pH.
7. Amount of fat in body.
8. Constituents of diet.
9. Physical activity and other stresses.
Biochemical differences among species (Table 4) are due primarily to
enzyme variations. These enzyme differences are not only important
because of the differences in digestive tract organisms and their enzymes,
but also because of variations in the level of circulating enzymes and
in the activity of enzymes in the liver and kidneys. In order to deal
with such variations specifically, one would have to identify the specific
biochemical pathway important for metabolizing the foreign chemical under
consideration and then determine the activity of that pathway in the
68
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specific exposed species of animal. This is a complicated and time
consuming process; hence little information of this nature is available
for each of the common animal species, including man. However, investi-
gations in this area are fruitful and it is potentially one of the most
dynamic and rewarding areas for biochemical and toxicological research.
Comparative studies are not only important in infectious diseases, but
they are being seen as of at least equal value for chemical disorders.
TABLE 4 •;
Biochemical Species Differences
1. Digestive tract enzymes
2. Level of circulating enzymes
3. Liver enzymes
4. Other degradative processes •
: Adverse Effects
Although "poisoning" usually refers to an acute overdosage or severe
response to a foreign chemical, there is another area, "adverse effects,"
that is much broader in definition and may include poisonings. Table 5
presents a listing of some common adverse effects.
TABLE 5
Adverse Effect vs. Poisoning
1. Poisoning refers to acute overdose or sensitivity.
2. An adverse effect is any one of a number of addi-
tional reactions, which may include poisoning.
a. "Side effect"—other than expected response
b. Immune reaction
c. Interaction with other compounds
d. Enzyme inhibition or induction
e. Carcinogenesis
f. Mutagenesis
The commonly referred to "side effect" is usually nothing more than a
biological reaction to a foreign chemical that is different from that
normally expected. This reaction may be a form of toxicity or it may
be an exaggerated physiological response due to reactions with receptors
or body tissues other than the normal target organ. Adverse effects may
be due to antigen-antibody or immune reactions. Sensitivities to foreign
chemicals and anaphylactic reactions fall in this category. Chemical
interactions are capable of producing a wide variety of adverse effects
69
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by blockade or interaction with receptors, alterations in enzyme activity,
interference with enzyme systems, or by producing cellular reactions
resulting in altered organ function and chemical elimination.
Enzyme inhibition or induction is a recently found but well-documented
syndrome (1,4). This very interesting series of reactions results in
decreased or increased enzyme activity due to concurrent or prior expo-
sures to foreign chemicals. Inhibition is due to chemicals blocking
enzymatic pathways and reducing the rate of metabolism of foreign com-
pounds; hence prolonged response or toxicity due to the toxic material
results. Induction results in increased enzymatic activity, with
increased metabolism of not only the previously administered chemical,
but also of other foreign compounds metabolized by the same enzymatic
pathways. The result i;s more rapid biotransformation and excretion, a
shorter biological response, and usually decreased toxicity. Excellent
detailed descriptions of these phenomena are available to interested
scientists (1,4-7).
The development of cancer and the production of congenital anomolies are
two subtle but extremely important adverse effects that may result from
exposure to foreign compounds. Both are difficult to reproduce experi-
mentally, and clinical evidence incriminating specific chemicals in either
condition is usually vague and, at the best, suggestive. The factors
involved with cancer production are incompletely described (1), but the
current national interest in this increasingly common health problem has
resulted in the establishment of a national program to deal with cancer.
Not only is the National Cancer Institute being rapidly expanded, but a
major portion of the research effort at the newly developed National
Center for Toxicological Research is devoted to the study of potentially
carcinogenic chemicals. There is no doubt that a massive attack is being
mounted on the problem of cancer; how productive it will be remains to be
seen.
Mutagenesis and Teratogenesis
The appearance of birth defects is the outward evidence of a mutagenic or
teratogenic effect of exposure to a foreign compound during pregnancy.
This adverse effect is perhaps the most subtle and yet the most critical
of all the potential problems that might develop from foreign chemical
exposure. Not only are the observed defects first seen only months after
the exposure and resulting cellular damage have occurred, but sterility
of gametes, death of the fertilized but unborn organism, or abortion also
may result. From a clinical standpoint, these latter three end-effects
are largely undiagnosable, if indeed they are even observed.
Figure 1 diagramatically presents the potential effect of teratogenic
agents on gametes and various stages of prenatal development. Agents
affecting gametes commonly produce sterility, but if viable gametes
result, no effects on the fertilized product are seen. Chemicals present
during the blastocyst stage (the fertilized unimplanted organism) common-
ly produce death of the organism, or they produce no effect and a normal
individual. The embryo stage (implantation has occurred and cell differ-
entiation is in process) is most susceptible to chemical interferences
70
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causing major structural abnormalities or defects. Death is possible
but less common than during the earlier periods. During the stage of
the fetus (differentiation is largely complete and organ growth occurs),
the incidence of death is low and major structural abnormalities do not
occur at a significant level. Abnormalities in organ function can result
from exposure to foreign chemicals during this stage, but the fetus is
relatively insensitive to foreign compounds and a normal individual
usually develops.
STERILITY
Figure 1.—Schematic representation of the influence of terato-
genic factors on gametogenesis and various stages of prenatal
development. Strong teratogenic agents—wide arrows; weak
teratogenic agents—narrow arrows.
It is thus seen that the period of the embryo is the most critical stage
for the unborn individual and that this is the period during which
congenital defects or major structural abnormalities are most likely
to result following exposure to teratogenic chemical factors. This
particular period is crucial because of the sensitive condition of the
differentiating cells of the growing organism. Each organ undergoes
differentiation during a specific phase of this period; hence exposure
to chemicals during the period of differentiation of the heart results
in heart abnormalities, while exposure to chemicals during the period of
oral cavity development results in defects of the oral cavity. The type
of defect observed permits a judgment as to the time during which the
teratogenic factor was present in the developing organism.
Table 6 summarizes the syndrome of mutagenesis and teratogenesis. The
production of a structural or functional defect is the most common, but
not the only, result. While a wide variety of causative agents may pro-
duce a defect, chemicals are one of the more important etiological factors,
and they appear to be becoming more significant with the increased use of
chemicals in everyday activities and their presence in the environment.
Any one of the reproductive stages may be involved in this syndrome,
either through direct effects upon the gamete or rapidly growing and
dividing cells, through the production of toxic metabolites and their
7l
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effects on growing cells, by altering nutrition to the growing organism,
by producing variations in cell division and growth, or by the inter-
actions and aynergistic effects of several of the above factors. The
subtleness of this problem and the difficulty in relating a cause to
the end product not only makes this syndrome difficult to clinically
interpret, but research and the documentation of causative factors are
subject to much controversy. This problem will continue to be of major
concern for many years.
i
TABLE 6
Mutagenesis (Teratogenesis)
1. Production of structural or functional congenital defect.
2. Wide range of causative agents.
3. May affect gamete, blastocyst, embryo or fetus.
a. Direct effect i
b. Through metabolites
c. By altered nutrition
d. Through variations in cell division and growth
e. By synergistic effects of several factors
4. Subtleness of effect causes much concern.
Sites of Chemical Action
The variety of chemicals that may cause toxicity, adverse effects, or
participate in chemical interactions is abundant. Equal in variety are
the biological sites at which these chemicals may produce their action.
All produce their effect by reacting with one or more cellular components,
and as illustrated in Figure 2, the "typical" cell has numerous foci at
which chemicals may initiate a toxic or adverse effect.
The first cellular structure that a foreign chemical contacts is the cell
membrane or wall. Here the chemical may cause coagulation of proteins or
may inactivate vital enzymes responsible for maintaining the integrity of
the cell. Protein precipitation or enzyme inactivation results in not
only the cell losing its integrity, but also allows penetration of the
foreign chemical into the innermost portions of the cell. Once inside
the cell membrane, the chemical may react with several intracellular
structures. The endoplasmic reticulum, containing ribosomes, is respon-
sible for the metabolism of naturally-occurring and foreign compounds;
proteins and enzymes synthesized by the ribosomes produce the catalytic
activity for biotransformation. The presence of toxic amounts of a
foreign chemical may result in altered protein and enzyme production
and a decrease or cessation in the cell's capacity for biotransformation.
The lysosome contains packets of enzymes responsible for digesting
foreign material introduced into the cell. The digestive enzymes (lyso-<-
zymes) are kept within the isolated packets until required by membranes
72
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C Y T O P L A S M
ENDOPLASMIC
\ RETICULUM
^^^
Figure 2.—The schematic cell.
73
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similar to those surrounding the cell. A foreign chemical which has
already penetrated the cell membrane may also disrupt the integrity of
the lysosome membrane and lead to release of the digestive enzymes into
the cell is cytoplasm. Self-digestion or autolysis is the usual result.
The mitochondria are the generators of the cell and produce the energy ,
required to keep cellular function at a normal level. The electron
transport system, oxidative phosphorylation, and the production of ATP \
are all actively involved with the mitochondria. Foreign chemicals
within the cell may enter the mitochondria and disrupt their energy-
producing capability, resulting in "short-circuiting" the cell and power
failure. A cell without energy cannot function and death is imminent.
The nucleus is the central portion of the cell and contains the genetic
material enabling reproduction and the ability to form normal daughter
cells. Foreign chemicals entering the nucleus are capable of disrupting
the genetic material (chromosomes), resulting in complete loss of repro-
ductive ability or altered capacity to produce normal cells. In the
latter instance, abnormal cells may develop and lead to the production of
tumors, or in developing individuals, birth defects (teratogenesis) are
the visible outcome.
In all instances, interaction with these cellular sites causes a disturb-
ance of some vital portion of the cell, leading to altered cellular
function and frequently death. The particular cell or cells affected
vary with the route of chemical exposure and the specific sensitivity of
the various body tissues to the particular chemical or chemicals intro-
duced. The affected cells may be in the liver or kidney, or they may
be red blood cells. Enzymes, in the brain or elsewhere, may be affected.
On occasion, the protein of digestive tract cells may become severely
coagulated and destruction of the intestinal tract lining becomes a
prominent clinical effect. The specific affected cell and the resulting
clinical signs, however, are largely determined by the characteristics
of the chemical within the system. The basic effect is biochemical
alteration of cellular function; the altered functioning results in i
physiological changes that are observed as signs and symptoms of toxicity.
Health Implications
The implications of the existence of one or more foreign chemicals within
the body is thus apparent. Increased or decreased effects of therapeutic
or environmental agents may result from the concurrent presence of other
intentionally or accidentally introduced substances. The increased effect
of a chemical due to interactions with other biologically present compounds
may result in increased patient response and adverse effects or toxicities.
Adverse effects, those reactions for which the clinician is unprepared
since they are not expected, may produce life threatening emergencies
because they are frequently unrecognized until clinical signs become
severe. The onset of signs is frequently sudden, making effective treat-
ment additionally difficult.
Chemical interactions resulting in a decreased effect of foreign chemicals,
such as therapeutic agents introduced for a positive disease controlling
response, may complicate and even nullify any useful purpose of the drug.
-------
This unexpected lack of effectiveness in a therapeutic agent is usually
unrecognized for several daySj at which time the patient is noticed
failing to respond or worsening. If these frank chemical interactions
leading to acute effects are difficult to diagnose and compensate for,
the problem of the more subtle interactions, resulting in immune situa-
tions, chemical resistance, tumor and cancer formation, or the after-
the-fact observation of embryonal death and birth defects, can easily
be seen to present much more complicated and confusing clinical problems.
Their clinical recognition is only the first step. Understanding the
mechanisms and specific chemical-biological interactions producing these
consequences is a task that will require large scale dedicated and
conscientious effort.
Even what little is currently known of the interactions involved in the
"normal" processes of chemical metabolism and excretion is a vast amount
of material (1-4,7-9). Figure 3 is a simplified illustration of some of
the more significant interrelationships that occur in the biotransforma-
tion processes of any single given chemical. How much more confusing the
scheme would be if all the known details of the interrelationships were
included. How infinitely more complex the entire picture would be if we
were to include the interactions possible when two or more foreign
chemicals were present and competing for the same processes. Interested
individuals are encouraged to consult the publications listed in the
references for a review of the basic information currently available
about chemical interactions (1-9).
Mechanisms of Chemical Interactions
From the available literature, it is possible to speculate about the
mechanisms that control and affect chemical interactions (3,6). The
major types of such mechanisms are outlined in Table 7.
TABLE 7
Possible Mechanisms Affecting Chemical Interactions
1. Direct effect or chemical reaction between agents.
2. Modified biodynamics and detoxication.
a. Altered intestinal absorption.
b. Altered topical absorption.
c. Unusual biological distribution.
d. Modified action at receptor site.
e. Altered biotransformation.
f. Altered pattern of excretion.
3. Potentiation or inhibition.
4. Modifying physiological variables.
5. Interaction of environment.
6. Multiplicity of mechanisms.
75
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Figure 3. Interrelationships between various biotransformation processes
TISSUE
BOUND Z=±FREE«
SITE OF ACTION
"RECEPTOR"
FREE
BOUND
PLASMA
BOUND DRUG
METABOLITES
EXCRETION
METABOLISM
-------
A direct effect of several chemicals on receptors or various cellular
sites is the most obvious possible mechanism. Chemical reaction between
two or more compounds present in the system, resulting the potentiation
of effects or canceling of one or more of the chemical actions, are also
apparent direct actions that might occur. Much of the information
available about these direct effects is the result of extrapolation of
information about individual chemicals, their direct actions, and their
interactions with cellular materials and other chemical compounds. Some
of this information has been documented in patients; other aspects remain
to be shown of clinical significance.
A very important and multifaceted potential mechanism for chemical inter-
actions is the possible effect of several chemicals modifying the normal
biodynamics and detoxification processes of the body. Variations in
intestinal absorption may result from alterations in digestive tract pH,
variations in intestinal motility and bacterial flora, chemical complex
formation within the digestive tract that results in nonabsorbable salts
and other inert compounds, complex formations that produce osmotic
effects, complex formation resulting in sequestration of chemicals as
lipoid materials or precipitates, alterations in the digestive tract
mucosa, effects upon transport systems and mechanisms within the digestive
tract, and circulatory alterations due to chemical interactions in the
intestinal tract.
Similar alterations in absorption may occur if the chemicals are applied
topically and the effects previously cited for the digestive tract occur
in the mechanisms responsible for absorption through the skin.
Modifications in pharmacodynamics will exert their effect upon the normal
pattern of foreign chemical distribution within the body. Transport
systems, such as those active in the flow of physiological fluids, physi-
cal factors within membranes and transport systems, and specific transport
across membranes may be altered. The presence of multichemicals within
the system may result in displacement of one or more chemicals from
binding sites or from storage tissues. Thus distribution alterations
result in effects upon transport systems or upon storage or binding sites
due to chemical-chemical or chemical-tissue-chemical interactions.
Additional modification may occur at receptor sites responsible for normal
biological responses. Competitive inhibition, physiological antagonism,
or nonequilibrium-noncompetitive antagonism may occur at cholinergic or
adrenergic receptors. One or more of the foreign chemicals may act as
partial agonists. These multi-actions can result in a variety of alter-
ations from the expected receptor response.
When more than one foreign compound is present within the system, the
biotransformation systems responsible for altering and detoxifying these
foreign chemicals may become saturated or in other ways be forced to
alter normal metabolic pathways. Enzyme inhibition and enzyme induction
may effectively increase or decrease the duration of action and effect
of a foreign compound. Other complex mechanisms, as yet undescribed, are
also potentially possible.
77
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The excretion of a foreign compound is usually a reliable means of ending
that chemical's effect upon the body. Alteration in the pattern of
excretion may markedly affect the length of time and effect that a
foreign compound may exert upon the body. Multiple chemicals within the
system may alter the urinary pH, have a direct effect upon the kidney
tubules (thus changing expected absorption or secretion patterns within
the tubule), or cause complex reactions involving more than mechanism to
occur.
Chemicals reacting between themselves may cause potentiation or inhibition
in the effects of one or more of the compounds present. Further, physio-
logical factors that commonly would determine a chemical's influence upon
the body may be altered by other chemicals being present at the same time.
Factors such as age, body temperature, nutritional and pathological state,
sex, species, and genetic make—up may all be modified by the presence of
additional chemicals.
The interactions produced by environmental factors have not received
great attention. From the nutritional standpoint, diet and influence of
carbohydrates, proteins, minerals, vitamins, and water upon simultaneous-
ly ingested foreign chemicals is an obvious factor that has long been
overlooked as influencing the effect of foreign chemicals. Even ambient
temperatures and whether the subject is housed in a cold, normal, or hot
relative environment may greatly influence body metabolism and activity;
hence, it could play an important role on the effect of circulating
foreign chemicals.
Like so many biological reactions, it is likely that no single mechanism
or explanation will be ultimately found to be the only significant one.
It is more plausible that a multiplicity of mechanisms, involving many
or all of those heretofore theorized, are actually working to influence
chemical interactions. The specific identification of these mechanisms,
however, is currently a great goal for relevant and important investi-
gations .
All health scientists await, and hopefully are "doing their thing" to
contribute to, answers to these vital questions. Without documentation
and understanding of how the presence of more than one chemical within
the system will influence that system's functioning, man and animal are
at the mercy of the therapeutic and environmental agents so frequently
applied to patients and the general population. By understanding these
interactions and the factors that govern them, health scientists and
clinicians will be taking a giant step toward reducing the hazard from
foreign chemicals.
An awareness of this increasingly common chemical syndrome is required
to hasten the development of the capacity to treat and eventually prevent
chemical interactions. It is hoped that this review will stimulate a few
inquiring individuals to pursue this problem and to strengthen the
painfully limited information currently available.
78
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Summary
Chemical interactions are those biological responses not expected, but
frequently observed, when two or more foreign chemicals are present in a
biological system at the same time. As increasing numbers and varieties
of foreign compounds are superimposed upon the body, it is understandable
that undesired reactions are becoming more frequent. The presence of
two or more compounds in the body may result in a decreased biological
response, an increased biological response, or a new unexpected toxic
reaction. These biological responses may be the result of receptor-
chemical blockade or interaction, enzyme inhibition or induction, inter-
ference with enzyme systems, or cellular reactions resulting in altered
organ function and chemical elimination. Since most interactions are
not well-documented and even less understood, the clinician may suddenly
be faced with an unexpected response to his patient. His reaction,
whether to increase or decrease the administered dose, attempt antidotal
therapy, or do nothing but observe and monitor vital signs, may be vital
to the outcome of the case. Many clinicians accept such unexpected
responses and discard their significance as an "individual variation."
There is a definite need and responsibility to recognize document, and
attempt to understand these chemical interactions in order to prevent and
control the unfortunately frequent life-threatening episodes that may
result.
References .
1. Goldstein, A., L. Aronow, and S. M. Kalmam. Principles of Drug Action.
Harper & Row, N. Y. 1968.
2. Gourley, D. R. H. Interactions of Drugs with Cells. Charles C.
Thomas, Springfield, 111. 1971.
3. Hansten, P. D. Drug Interactions. Lea & Febiger, Philadelphia. 1971.
4. La Du, B. N., H. G. Mandel, and E. L. Way, Editors. Fundamentals of
Drug Metabolism and Drug Disposition. Williams & Wilkins, Baltimore.
1971.
5. Martin, E. W. Hazards of Medication. J. B. Lippincott, Philadelphia.
1971.
6. Moser, R. H. Adverse effects and interactions of drugs. In Remington's
Pharmaceutical Sciences, 14th ed. A. Osol, Editor. Mack Publishing,
Easton, Pa. 1970. pp. 1381-1401.
7. Stolman, A. Combined action of drugs with toxicological implications,
Part I. In Progress in Chemical Toxicology. Volume 3. A. Stolman,
Editor. Academic Press, N. Y. 1967. pp. 305-361.
8. Stolman, A. Combined action of drugs with toxicological implications,
Part II. In Progress in Chemical Toxicology. Volume 4. A. Stolman,
Editor,, Academic Press, N. Y. 1969. pp. 257-395,
9. Swidler, G. Handbook of Drug Interactions. Wiley-Interscience, N. Y.
1971.
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EXPOSURE MEASUREMENT
Anne R. Yobs
Exposure measurement is not a new problem, nor is it restricted to
chemical pollutants—although certainly the term has been extensively
bruited about in connection with environmental considerations recently.
The physician and public health personnel who work with infectious
diseases have been measuring exposure since it was first realized that
certain clinical entities are caused specifically by infectious agents
and since laboratory procedures were developed for diagnosis of exposure
to these agents. These include culture, microscopic examination of
parasite or tissue, hematology and serology tests and certain measure-
ments of physiologic change. As we will discuss in greater detail
later, exposure to chemicals is usually measured with other procedures,
although at times these same procedures may be used. The importance of
accurate exposure measurement is pointed out by the following definition
of epidemiology:
Epidemiology has been defined as a science of mass phenomena.
It describes significant varieties of the phenomena in time
and place. It draws upon statistical methods and theory, all
phases of medicine and the natural sciences to give a true
picture of the occurrence, distribution, and types of defects.
The proper use of this material, however, requires that it be
carefully and accurately collected by reliable individuals
who are able to describe what they observe. It must also be
recorded in such a manner as to be recoverable when required
alone, or to be synthesized with other material for future use.
The objective of an epidemiologic study or investigation is
to determine the circumstances that have led or will lead to
selective exposure of certain individuals in a population to
those factors—whether infectious, chemical or physical—
that result in the development of an illness or abnormality.
Successful study not only leads to understanding and identi-
fication of etiologic agents but should also reveal one or
more alternatives for prevention. Thus, the epidemiologic
approach is different from but related to clinical and bio-
statistical studies of disease and to preventive programs.
Successful epidemiologic study requires the accurate identi-
fication of exposure and of cases to insure that cases in the
group under study represent the same problem. In addition,
characteristics of the case series may be compared with traits
of an unaffected group or area where there is no problem and
it is assumed there is little or no risk.
Let's restrict our attention to environmental pollutants and consider
the value of exposure measurement information before discussing specific
details of procedures required for its development. Exposure, that is
contamination, may be measured in any environmental substrate. This
data when combined with certain other information about production,
usage, i.e., introduction into the environment, etc., makes it possible
to define distribution and trace movement (of the material) through the
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parts of the environment as well as on a geographic basis. This mass
of information is also necessary to the evaluation of environmental
quality at a given time and changes over a time interval; this evaluation
permits determination of the impact of certain regulatory decisions and
enforcement actions or other occurrences. On an individual basis, this
type information is useful in evaluating—and improving-^-working condi-
tions in selected industries and in the diagnosis and treatment or
prevention of acute or chronic poisoning.
Exposure measurement would be relatively easy to accomplish if available
methodology permitted use of the same approach in investigating varying
problems and pollutants and if the amounts involved in exposures were
larger.
Exposure may be measured in several ways; however, no one way is
applicable to all problem situations; each is suited to some selected
situations and not to others. These methods may be divided into two
groups: direct and indirect. Either may apply to individual or ambient
measurements. Direct exposure measurement is the quantitation of the
chemical or its metabolites contained in a sample of an environmental
substrate such as air, water, soil, and food products. It may also be
used to determine surface contamination of plants, animals, or man, or
to estimate prior or current exposure by measuring the amount of a
chemical, or its metabolites, which is present in the body or which is
excreted from the body. Indirect exposure measurement requires quanti-
tation of specific physiologic effects known to occur as a result of
exposure to that chemical, such as enzyme induction or inhibition, change
in nerve impulse transmission or cardiac rate, change in organ function,
or induction of abnormal growth, etc. These changes must be specific
for the chemical or chemicals under consideration.
Entirely different laboratory facilities may be required for the differ-
ent methods and when the same method is applied to different chemicals.
Direct exposure measurement and measurement of storage or excretion
levels generally call for an analytical chemistry laboratory facility
and competence, while measurement of physiologic effects may require an
entirely different type laboratory facility. For instance, in studying
exposure to the pesticide parathion, the parent chemical may be measured
directly or urinary excretion of the metabolite para-nitrophenol or the
alkyl phosphate metabolites may be measured; these all require an
analytical chemistry laboratory with gas liquid chromatograph and flame
photometric detector. On the other hand, if parathion exposure is
measured in terms of cholinesterase inhibition, a biochemistry laboratory
is needed; and if in terms of nerve impulse transmission, a neurology
laboratory with electroencephalograph is required. Similarly, exposure
to radioactive materials may be measured directly or indirectly and a
pathology laboratory may be required instead of a scintillation counter
laboratory.
In the field and in most research situations, it is not possible to use
all available methods for exposure measurement nor to perform exhaustive
studies to determine total exposure. That method must be chosen which is
most appropriate to the problem by virtue of applicability, sensitivity,
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specificity, possible routes of exposure and restraints of available
laboratory facility, staff competence and financial support. Routes of
exposure vary with species and substrate, for example:
Man & animals Ingestion Respiration Topical (dermal)
Fish Ingestion Topical
Soil Topical
Plants Root absorption Topical
Water Direct introduction
Air Direct introduction
The significance of the route depends on the chemical, the dose, and
the time interval of exposure.
Problems associated with exposure measurement will differ with the
situation being investigated. These may be identified as follows:
Ambient Research
Individual specific Field
ambient incident
occupational survey
poisoning
Ambient studies may be directed to one or a wide range of pollutants.
Generally, levels encountered in ambient surveys are quite low and their
variety may be broad. This is true to a lesser degree in ambient studies
of a specific individual or location. Occupational or poisoning studies
may be somewhat less difficult because higher levels are involved and
because it is frequently possible to identify the specific pollutant
through field investigation before samples are sent to the laboratory.
The availability of such information greatly simplifies the problems
of sample collection and laboratory analysis.
Field studies may also be directed to one or a wide range of pollutants;
this is especially true for field surveys but may also apply to incident
investigations. In the latter case, levels of specific pollutants en-
countered are usually higher than in surveys, but it should be recalled
that ambient levels of pollutants are present in addition to the suspect
pollutant(s).
In research studies, it is possible to limit the scope of activity to a
restricted area and to use a maximum amount of time in developing data.
It should be noted that currently the measurement of man's total exposure
to many pollutants would of necessity be a research project. It is
entirely conceivable that in the future the further development of
sensors will simplify this problem.
All exposure measurement studies require careful preplanning, as well as
consultation with field and laboratory personnel on a variety of topics:
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1. Determination of goals: Can they be recalled? Will this be a
negative study? A false positive study? How many samples are
needed; what frequency?
2. Location of sampling sites and establishment of sampling
schedule: What sampling techniques will be used? Is it simple
or sophisticated? Will it retain the pollutant of interest?
Who will collect samples? Is training needed? What are the
requirements for sample containers and sample transport?
3. Analysis: Is the identity of the material of interest known or
suspected? Is methodology available for this material? Is it
both sensitive and specific enough for the problem? Will the
sampling technique have to be one that will concentrate the
pollutant? Is the laboratory staff competent in the analytical
procedure? Equipped? Is the material stable? What is the
mazimum allowable time between sample collection and analysis
for data to be valid? How much confidence do you have in the
laboratory—internal quality control, interlaboratory quality
control (reference laboratory), instrument maintenance? Are
suitable reference standards available? What interferences
might be encountered? What confirmatory techniques will be
used?
A. Data evaluation: Is data to be combined from other laboratories?
Other studies? Other methodologies? Use extreme caution in
interpretation. Who will evaluate data? How?
Failure to consider each of these points fully will jeopardize the success
of the study.
It is obviously impossible to speak to each of these points for all con-
ceivable pollutants within the allotted time and space. To do so would
be misleading in the future because of the rapid developments being made
in environmental techniques. Therefore, it is recommended that thorough
library research and consultation with individuals knowledgeable in the
field be performed as the first step in studies involving exposure
measurement.
In summary, exposure measurement is required for proper case or problem
identification or for problem prevention. It is critical in toxicologi-
cal matters where there are definite relationships between time and dose
and the development of effects. Exposure may occur by several routes and
may be measured in several ways; however, no one way is applicable to all
situations, each being suited to some situations and not to others. Suc-
cessful studies in the area require teamwork and careful planning at all
stages.
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PCB'S IN HUMANS
Anne R. Yobs
j
The polychlorinated biphenyls (PCB's) were described in the literature
in 1881 (7), but they were not formulated and fully developed for in-
dustrial use until 1930. The PCB's (trade name Aroclors in the U.S.A.,
Phenoclor in France, Colphen in Germany, and Kanachlor in Japan) are
manufactured in the U.S.A. primarily by Monsanto Chemical Company. The
basic structure of PCB's is shown below where "x" represents any number
of possible positions for chlorination leading to about 210 possible
combinations, of which 102 are probable. Widmark, who made this cal-
culation in developing criteria for these limitations, noted that the
criteria were based on compounds containing five to eight chlorine atoms
per molecule, the number of chlorine atoms per ring differing by not more
than one (8) . ~ ~
The Aroclors may consist of chlorinated biphenyls, chlorinated terphenyls,
or a mixture of these compounds. Invariably, although a specific num-
bered Aroclor may represent a molecular type and degree of chlorination
or weight percent of chlorine, the product is in actuality a mixture of
several of the compounds in a series. The first two digits represent the
molecular type and the last two digits give the weight percent of chlo-
rine. For example:
1200 = Chlorinated biphenyls
2500 = Blend of chlorinated biphenyls and
chlorinated terphenyls (75:25)
5400 = Chlorinated triphenyls
The Aroclors are chemically inert, making them ideally suited for certain
industrial uses. They are not hydrolyzed by water, and they resist
alkalis, acid, and corrosive chemicals. Since they are not volatile,
their "boiling points range from 278°C to 451°C. They are stable to long
heating and can be distilled at ordinary pressure without any carboniza-
tion or decomposition. As might be expected since they are insoluble in
aqueous media, they are quite soluble in hydrocarbon solvents. It is
believed that PCB's are more stable than DDT and metabolites and, accord-
ingly, resistant to biodegradability or biological decomposition.
PCBs and formulations thereof have a wide range in viscosity and physical
state. Other properties such as low solubility in water and high di-
electric constants make them versatile for industrial uses. Many of
these PCB preparations have strong adhesive properties. Aroclors could
be used to extend the effectiveness or lethality of organochlorine in-
secticides such as chlordane, aldrin, and dieldrin in pesticidal formula-
tions .
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PCB's have been in use for more than four decades, not only in the United
States but throughout the developed world. The physical and chemical
properties that make polychlorinated compounds valuable industrially
assure their ability to become serious persistent environmental pollution
hazards. These properties include high boiling points, low water solu-
bility, high dielectric constants, miscibility with organic solvents and
polymers, remarkable thermal stability and resistance to chemical degra-
dation. Industrial uses may be classified as "closed" or consumptive.
Closed systems include electrical capacitors and transformers, heat
transfer systems and hydraulic fluids. Consumptive uses involve synthet^
ic rubber, paints, plastics, wire insulation, caulking material, flame
retardants, cutting oils, pesticide synergists, adhesives, sealants,
paper printing inks and protective coatings for wood, metal or concrete.
Inadvertent environmental contamination can occur accidentally from
closed systems, but environmental infiltration is inherent in the con-
sumptive uses.
Data on sales of PCB's are available only for the United States from
1957 to 1971, with sales reaching a high of 36,000 tons in 1970. Sales
doubled from 1960 to 1970; assuming the same growth rate from 1930 to
1970, about 500,000 tons have been sold in the United States. Data from
outside the United States are few. It is estimated that Japan manufac-
tured 13,000 tons per year (3). PCB's are also produced in West Germany,
the United Kingdom, Spain, France, Italy, Russia, and possibly new pro-
ducers in Brazil, Argentina, India, and East Germany. Assuming that the
United States used half of the world total, world production would have
been about one million tons—approximately half the estimated total pro-
duction of DDT. Monsanto's 1971 sales dropped to half the 1970 level,
and 1972 sales are expected to be 12 to 15,000 tons. Prior to 1971, when
Monsanto (the sole U.S. manufactorer) curtailed sales to non-closed
system uses, about 40 percent was used in plasticizers, hydraulic fluids
and lubricants, surface coatings, inks, pesticide extenders, and micro-
encapsulation of dyes for carbonless duplication paper—uses that
potentially result in environmental contamination.
If the same percentages held worldwide, 40,000 tons might have been used
in ways that could easily reach the environment; accidents and careless
disposal practices would have increased this amount considerably, perhaps
to 50,000 tons or more.
Nisbet and Sarofim (6) provided rough estimates of the losses of PCB's to
the North American environment in 1970: 1500 to. 2000 tons to the atmos-
phere (mostly Aroclor 1254 to 1260 from plastics and 1242 from burning
dumps); 4000 to 5000 tons to fresh and coastal waters (Aroclor 1242 to
1260); 22,000 tons into dumps and landfills (mostly Aroclor 1242). Other
losses were judged to be small, but often locally significant. The total
loss to the North American environment from 1930 to 1970 was estimated to
be:
Atmosphere 30,000 tons
Water - fresh and coastal 60,000 tons
Dumps and landfills 300,000 tons
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The total of 390,000 tons is within a factor of two of the above estimate
of 500,000 tons that might have reached the world environment. They
further estimated that one-third of the PCB's released to the air and
one-half of those released to water have now been degraded. The PCB's in
dumps probably have undergone less degradation.
Given the diversity of uses of PCB's and their chemical stability (great-
er stability in the higher chlorine species), it is not surprising that
residues are now widespread. While satisfying quantitative estimates of
the contribution of various pathways into the environment are not possi-
ble with existing data, there are enough data to be certain that they do
reach the environment at least from the following sources:
— Open burning or incomplete incineration (at usual tem-
peratures) of solid wastes, municipal and industrial.
Incineration at 2000°F or above for two seconds will
destroy PCB's, but poorly operated incinerators or open
burning may result in PCB's being released unchanged to
the atmosphere.
— Vaporization from paints, coatings, plastics, etc.
Nisbet and Sarofim (6) estimate that as much as 20 per-
cent may be vaporized.
— Municipal and some industrial sewers (present in treated
as well as untreated wastes). See Tables 2 and 3.
— Accidental spills or improper waste disposal practices.
— Formerly, direct application to the environment as in-
gredients of pesticides or as carriers for pesticides
(such uses are now prohibited).
— Dumping of sewage sludge, municipal and industrial solid
waste, and dredge spoil at sea.
— Sewage sludges disposed of on land.
— Migration from surface coatings (paints, etc.) and pack-
aging materials into foods and feeds.
Probably the largest amounts of PCB's circulating in the environment
reach it through industrial and municipal discharges to inland and
coastal waters. They were not recognized as environmental contaminants
until 1964-1966 when Jensen in Sweden identified a series of unknown
peaks on gas chromatograms of pesticide analyses as these substances (4).
These first identifications were in fish and bird tissues; examination
of other samples soon revealed that PCB's were widespread in biological
materials. Existing data suggest tihat although the greatest concentra-
tions of residues are found in the Vicinity of industrial and municipal
areas in the Northern Hemisphere, residues exist in areas remote from
civilization and in both the Northern and Southern Hemispheres.
In 1971, the PCB's were included routinely in the list of chemical
residues for which every sample of human adipose tissue was routinely
analyzed in the Human Monitoring Survey (9). In this study, which was
initiated in 1967, samples are collected through the direct cooperation
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of pathologists who are in hospital or private practice or who are in
public service as city or county medical examiners. Samples are col-
lected from both sexes in all age and racial groups. Adipose samples are
collected from tissues removed for therapeutic surgery or from postmortem
examinations, the latter including people who have died accidentally
(trauma) or during relatively brief hospitalization. No samples are
accepted from institutions for long-term care of the chronically ill
patient.
All samples are analyzed by laboratories established under contract in
several states. These laboratories use analytical methodologies speci-
fied by the program and are required to maintain acceptable levels of
performance, as demonstrated in both inter- and intra-laboratory quality
control programs.
An analytical method was adopted which would separate PCB's from pesti-
cides permitting accurate quantitation of pesticides and confirmation of
PCB levels. This methodology is a further modification of the Mills,
Olney, and Gaither procedure in which adipose tissue is subjected to
extraction by petroleum ether, acetonitrile partitioning, and Florisil
cleanup. A portion of the resulting 6% ethyl ether/petroleum ether
eluate, in concentrate form, is treated with KOH to effectuate dehydro-
chlorination of DDT and ODD to their olefins, thus eliminating the
problem of separating these pesticides from the PCB's. Oxidative treat-
ment is then applied to convert any interfering DDE to p,p'-dichloro-
benzophenone which has an Rf value different from the PCB's. The PCB's
are then determined by thin layer chromatography.
Analytical results for 637 samples have been reported and are summarized
in Table 1. Of the 637 samples reported, 198 (31.1%) contained meas-
urable amounts of PCB's and 125 (19.6%) contained trace amounts, with
the balance being negative. These samples were collected from 40
pathologists in 38 cities distributed over 18 States and the District
of Columbia.
TABLE 1
INCIDENCE OF POLYCHLORINATED BIPHENYLS IN ADIPOSE
OF THE GENERAL POPULATION OF THE NATION
Reported
Negative
Trace (<1.0 ppm)
1 to 2 ppm
>2 ppm
TOTAL
No.
314
125
165
33
637
%
49.3
19.6
25.9
5.2
100.0
Positive samples came from every hospital, city, and state sampled. It
therefore appears that these materials are widely found in the population.
-------
Details of distribution by sex and race, collection procedure, and
diagnostic groups are summarized in Table 2. The difference between
figures for the positive and negative groups does not appear to be
significant, although no statistical evaluation has been performed
because of the small numbers in this report.
TABLE 2
DESCRIPTIVE STATISTICS OF SAMPLES ANALYZED
Negative and Trace
<1.0 ppm
Number
Percent
>1.0 ppm
Number
Percent
Sex
Male
Female
Race
White
Nonwhite
Samples from
Therapeutic surgery
Postmortem
Diagnostic group
Neoplasms 140-209
Circulatory
system 390-450
Gastrointestinal
system 530-565
Liver and gall
bladder 570-575
Pancreas 577
Urinary system
80-595
Congenital
anomalies 740-759
Accidents & violence
E numbers
All other
TOTAL
221
218
381
58
95
344
77
121
44
20
0
11
5
16
145
439
50.3
49.7
86.8
13.2
21.6
78.4
17.5
27.6
10.0
4.6
0.0
2.5
1.1
3.6
33.0
99,0
127
71
151
47
29
169
39
61
16
6
2
7
1
7
59
198
64.1
35.9
76.3
23.7
14.6
85.4
19.7
30.8
8.1
3.0
1.0
3.5
0.5
3.5
29.8
99.0
Finklea et al. have reported results of a 1968 study of residents of
Charleston County, South Carolina, distributed by race and residence.
Their findings are summarized in Table 3 (1). PCB residues were found
in parts per billion (ppb) concentrations in plasma. The prevalence of
PCB residues varied remarkably over race-residence groupings being great-
est in urban residents and rural whites. No clear independent age and
sex trends could be demonstrated. PCB residues were not linked to chlo-
rinated hydrocarbon residues commonly found in food and were only weakly
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linked to pesticide residues that might reflect recent household or
garden pesticide exposure.
TABLE 3
PCB RESIDUES IN PLASMA (PPB)
Rural Black
Urban Black
Urban White
Rural White
Number of
Observations
107
151
166
192
Range
0.0 -
0.0 -
0.0 -
0.0 -
20.6
29.0
22.0
16.6
Arithmetic
Mean
0.3
1.9
2.3
3.1
Because of their widespread industrial applications, their chemical
stability and persistence, and their ubiquitous presence in the ecosystem,
it is not unexpected that PCB residues have been detected in a variety of
food commodities. Several sources of contamination have been identified.
These can be generally divided into three categories:
1. Environmental contamination—background levels of PCB's in
fish from contaminated lakes and streams.
2. Industrial accidents—isolated incidents involving direct
leakage and spillage or contact of PCB fluids and other
PCB-containing materials on animal feeds, feed ingredients
or food.
3. Food packaging materials—PCB migration to foods packaged
in PCB-contaminated paper products. Identification of
these categories is not intended to imply that all posi-
tive PCB findings in food and other materials have been
successfully traced to any one of the three sources.
Samples have been reported where the cause of the PCB
residue was not clearly defined, and one could only specu-
late as to the source of the residue.
Since November 1969, FDA has analyzed for PCB residues all raw agricultur-
al commodities and other food classes sampled under its pesticide
surveillance program. More than 15,000 sample examinations had been
completed as of June 1971. A total of 279 of the objective samples was
reported to contain PCB's. An additional 200 food samples, collected as
follow-up samples of suspected lots because previous analyses indicated
a potential problem, were also found to contain PCB residues. PCB's were
encountered most frequently in fish, with 317 of the total positive
samples (479).
Compared to the chlorinated hydrocarbon pesticides, definitive aspects
of acute, sub-acute, and chronic toxicity still remain rather poorly
known. Chloracnegen effects were reported as early as 1936, following
industrial exposure to the PCB's. Occupational chloracne, however, has
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not been a problem with recent usage of the PCB's. Approximately ten
cases of fatal intoxication involving persons who handled or were ex-
posed to chlorinated biphenyls or naphthalenes in their occupations have
been described. In all cases, histological examination revealed liver
fatty degeneration, necroses and cirrhosis. It is important to note
that chlorinated naphthalene as well as chlorinated dibenzofurans have
recently been identified in two commercial polychlorinated biphenyl
samples (Phenoclor DP6 and Clophen A60) (2).
Human intoxication with the heat exchanger Kanachlor 400, a Japanese
manufactured PCS with 48 percent chlorine and containing as its main
components a tetrachlorobiphenyl and a pentachlorobiphenyl, was reported
in Western Japan in 1968.
More than 600 people were affected following the consumption of contam-
inated rice oil containing levels estimated to range from 2,000 to 3,000
parts per million PCB's (average of about 2,000 parts per million). Ex-
posure levels to the oil were calculated to approximate 15,000 milligrams
per day. The lowest reported figures allow an estimate of a minimal
positive effect level at 3 milligrams per day over several months. How-
ever, the average doses associated with significant disease in the
"Yusho" incident were much higher and were in the range of 30 milligrams
per day (5).
The clinical aspects associated with "Yusho" included: chloracne,
blindness, systemic gastrointestinal symptoms with jaundice, edema and
abdominal pain. Chloracne is very persistent with some patients showing
evidence of it after three years. Newborn infants born from poisoned
mothers showed skin discoloration due to transplacental passage of PCB's.
This skin discoloration regressed after 2 to 5 months. Gingival hyper-
plasia with pigmentation occurred in several cases. Decreased birth
weights were also noted but no evidence could be obtained in regard to
the possible retardation in physical and mental activities of the babies.
The skin of stillborn infants showed hyperkeratosis and atrophy of the
epidermis and cystic dilation of the hair follicles. Residues of PCB
were found in fetal tissue.
Components of Kanachlor 400 with longer retention times were detected in
sputa and fatty tissues of patients. Serum triglyceride levels were
higher than 300 mg/ml in 60 out of 396 subjects investigated before the
end of 1969. Among the incidence of hyperglyceridema (triglyceride
>300 mg/ml) of the six decade groups (age 0-9, 10-19, 20-29, 30-39, 40-
49, 50-), that of the first decade group was the highest while that of
the third decade was the lowest. The hyperglyceridema was considered to
be possibly due to decreased post-heparin lipolytic activity and impaired
plasma triglyceride removal. Cholesterol and phospholipid concentrations
were increased while lecithincholesterol acyl transferase activity was
decreased. In female patients, plasma lipoprotein lipase activity was
decreased, and steroid excretion was elevated.
Autopsy tissues of two Yusho fatalities contained chlorobiphenyls in all
organs examined, especially mesenterial fatty tissues, skin and bone
marrow. It was assumed that their presence might have been responsible
for the observed long duration of the intoxication symptoms (2).
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In summary, PCB's have been shown to occur at low levels in the general
population of the United States. The source of exposure to these chem-
icals has not been finally identified. Levels are far below those
reported in an epidemic poisoning which occurred in Japan.
References Cited
1. Finklea, J. et al. 1972. Am. J. Public Health 62(5):645-651.
2. Interdepartmental Task Force on PCB's. PCB's and the Environment.
ITF-PCB-72-1, p. 124.
3. Ispno, N. 1970. Jishu Kosa 1(1):60, 1(4):58.
4. Jensen, S. 1966. New Scientist 32:612.
5. Kolbye, A. C., Jr. Current Status of Toxicological Effects of PCB's
(FDA), Sept. 1 and Sept. 29, 1971.
6. Nisbet, I. and Sarofim, A. 1972. Environmental Health in Perspective
1, in press.
7. Schmidt, H. and Schultz, G. 1881. Ann. Chem. 207:338-344.
8. Widmark, G. 1968. O.E.C.D. - Sweden.
9. Yobs, A. R. 1972. Environmental Health Perspectives 1:1.
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EPIDEMIOLOGY OF POISONING BY CHEMICALS*
Frank S. Lisella
During the pre-World War II era, the hazards associated with the use of
many common chemicals went unheeded by the nations of the world.. In
1940, a British article was published implicating aspirin in 43 suicides,
8 accidental deaths, and 14 unclassified fatalities in Great Britain
during that year alone (2).
A series of accidental deaths from acetylsalicylic acid were reported
from the United States in 1950 (27). At that time, investigations re-
vealed that from 1926 to 1943 a total of 227 persons had died from the
consumption of excessive amounts of this chemical. These deaths were
associated with the increase in production of just one of the salicy-
lates—acetylsalicylic acid—which had exceeded 9 million pounds in one
year.
Medicants of various kinds have been shown to play a significant role in
childhood accidents and deaths. For example, oil of wintergreen was re-
sponsible for six deaths among children in England from 1931 to 1939, and
17 from 1940 to 1949 (50). The same chemical accounted for 28 deaths
among children in the United States in 1951, and 34 in 1952 (13). Other
products of concern have been broadly classified into categories such as
disinfectants, anti-septics, household poisons, poisonous plants, and
"miscellaneous."
A review of the accidental poisoning problem in the United States (5),
prompted by the findings of British investigator Douglas Swinscow (50),
revealed a total of 3,659 fatalities among children during the period
1940 to 1950. This represented a mortality rate four times greater than
that among children in England during the same period, which was attrib-
uted, initially, to racial differences between the two populations.
Medicants (drugs) accounted for approximately two-thirds of the cases in
England, but about one-third of the cases in the United States. In the
United States during the period 1949 to 1950, aspirin and the salicylates
caused a total of 113 deaths in children under 5 years of age; barbitu-
rates ranked second and accounted for 31 deaths. Iron poisoning, common
in England, is rare in this country, and only two cases were found in
this review. In one year, more than 100 deaths in the less than 5-year-
old group were due to ingestion of petroleum products, one of the major
factors responsible for increasing the rate in the United States over
that in England.
In 1953, a Scottish researcher reported on a detailed investigation of
poisoning episodes in that country (20) which showed that the number of
accidental poisonings seen at the hospitals in Edinburg had risen from
five cases in 1931 to 50 cases annually by 1951. This stimulated an
investigation into the accidental poisonings seen at the hospitals in
Edinburgh and Aberdeen, and the author reviewed 502 cases that occurred
during that period. The principal agents responsible for illness among
children in that study population are as follows:
* Reprinted from the Journal of Environmental Health, Vol. 34, No. 6, 1972,
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Agent No. of Cases
Disinfectants 39
Kerosene 31
Turpentine 25
Bleach 22
Barbiturates 36
Iron Preparations 24
Salicylates 20
Camphor 29
Laburnum 15
Concern about the problem of accidental poisonings in the United States
prompted creation of Poison Control Centers (15, 25). The first center
was established in Chicago in the latter part of 1953 and operated on a
city-wide basis. This center combined the efforts of the Departments of
Pediatrics of all five medical colleges in Chicago, the Chicago Board of
Health, the State Toxicological Laboratories, the Division of Services
for Children of the University of Illinois, and the six major teaching
hospitals in Chicago. An advisory committee that included representatives
of the American Medical Association, the National Safety Council, and the
Food and Drug Administration was formed. Each participating hospital was
provided with a summary of references on the basic toxic constituents of
the thousands of materials used in average households. Current knowledge
on treatment for ingestion of these materials was also made available to
each of the participating hospitals. A pediatrician was designated as
Poison Control Officer, responsible for liaison between the central com-
mittee and participating groups, assuring the availability of necessary
equipment and supplies in emergency rooms, orienting staff members to the
problems of poisoning, and reporting to the Chicago Board of Health.
By March, 1958, 124 centers were in operation in 40 states (15), and this
was increased to 580 centers in 49 states in 1960 (3). The general pur-
pose of the centers is to minimize the danger of toxic substances by
improving and expanding efforts for the prevention and treatment of poi-
soning.
In 1957, the Public Health Service reacted to the chemical poisoning
problem by establishing the National Clearinghouse for Poison Control
Centers (25). This group maintains detailed lists of the ingredients of
all household products and drugs and provides the information to the lo-
cal centers. Conversely, the local centers provide reports to the
Clearinghouse, on any new poison hazards they discover for dissemination
to all other centers. The Clearinghouse conducts research activities,
investigates and analyzes poison cases, and provides information on these
and other activities to the local centers through a monthly newsletter.
The Poison Control Centers provide the framework for detailed studies of
the chemical poisonings in many communities throughout the United States.
Scientific articles published since the Poison Control Center network
began include several dealing with epidemiologic analysis of case reports
submitted to the National Clearinghouse (11, 12) and others reporting
specifically on the chemical poisoning problem in selected metropolitan
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areas such as Chicago (43), New York (32, 34, 35), Salt Lake City (38),
and Syracuse (52, 55). One of these reports (12) was an analysis of
3,926 cases of accidental poisoning. The age group of 5 and under ac-
counted for 96 percent of the cases occurring in children under age 15
and 86 percent of the total. Males were reported to be involved in 53
percent of the total cases. Medicinal agents (aspirin, barbiturates,
non-barbiturate sedatives, tranquilizers) were the offenders in 2,152
cases (54.8 percent). Household preparations such as soaps, detergents,
and bleach accounted for 561 ingestions (14.3 percent), followed by
pesticides, 315 cases (8 percent); the remainder (22.9 percent) were
attributed to a variety of other products.
A paper by Howard M. Cann and colleagues reviewed in detail the results
of 15,094 individual case reports submitted to the Clearinghouse (11).
A similar pattern of age distribution was shown, with approximately 90
percent of the cases occurring in children less than 5 years of age.
Internal medicants were ingested in 41 percent of the accidents, and
aspirin was reported in over 50 percent of these cases. Where the type
of aspirin was known, the "baby" type accounted for 84 percent of this
total. Household cleaning and polishing agents were ingested in 17 per-
cent of all the accidents. Ten percent of all the reported ingestions
involved pesticides—the majority of which were insecticides. This
article differed from those previously published in that an attempt was
made to determine the type of container in which the ingested substances
were found at the time of the accident. In one-third of the total cases,
the chemicals were not found in the original container. Forty percent of
the poisoning accidents occurred in the kitchen, 22 percent in the bed-
room, and 12 percent in the bathroom; the remaining incidents occurred in
the basement, living room, garage, and other areas.
The report on the study in Chicago (43) showed the results of analysis of
1,033 cases of poisoning reported from 19 hospitals between December 1953
and May 1955. A pattern characteristic of that shown earlier was found.
Medicines were the primary agent, accounting for 523 (50.6 percent) of
the incidents; of these, 210 were attributed to aspirin, and 196 cases
involved cleaning, polishing, and sanitizing agents, with bleach the most
frequently ingested chemical in this category. Poisoning with pesticides
occurred in 107 (10.4 percent) of the total cases; insecticides were the
primary agent in this classification, followed by rodenticides. There
were six accidental deaths in children under 10 years of age, and six
fatalities in persons 22 to 48 years of age which could have been either
accidental or suicidal. In the majority of poisoning cases, the offend-
ing agents had been stored in the kitchen; in the remaining cases, they
had been kept in the bedroom, bathroom, and other locations, in that
order of priority. A predominance of the cases occurred among persons
residing in low socio-economic areas; however, the author admitted that
the possible bias in any conclusion drawn from this fact would be apprec-
iable.
Chemical poisonings, excluding those due to gas, are the third leading
cause of death in children under 6 years of age in New York City (32, 34,
35). In 1954, 454 cases of chemical poisoning occurred in children under
16 years of age in that city. Drugs were responsible for 47 percent of
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all poisonings, with aspirin as the principal agent and barbiturates as
the second leading cause in this category. Bleaches were the primary
agent in the household preparations class. Thirteen deaths were reported
among children as the result of ingestion of lead-based paints; this
finding corroborates similar investigations of lead-paint poisoning epi-
sodes in other areas of the United States such as Philadelphia (31),
Baltimore (45), St. Louis (47), Cleveland (49), and Chicago (17).
A 1955 study confirmed the problem of poisonings in children in New York
City (34). Twenty-one attempted suicides with chemicals were reported in
children ranging from 11 to 16 years of age. Eighteen were girls and
three boys. Age 13 was a high-risk category, accounting for nine inci-
dents. Aspirin was responsible for 10 poisonings, followed by barbitu-
rates, iodine, bleach, tranquilizers, antiseptics, and other agents.
While no fatalities were reported among this group, seven fatal cases
were reported in children ranging in age from 10 to 24 months.
A substantial increase in the number of poisoning incidents in New York
City between 1960 and 1961 (35) was attributed to improved reporting by
physicians. Sixty-six fatalities from poisonings occurred during this
period, with barbiturates as the chief cause. Ten fatalities from bar-
biturates, mainly suicides, were reported in the adult group. Six
fatalities occurred in children 5 years old, four from lead poisoning,
one from talcum powder ingestion, and one from cough syrup. The reported
number of cases rose from 5,070 for a six-month period in 1960 to 6,414
for the same time interval in 1961.
The study in Salt Lake City, Utah, in 1953 and 1954 revealed that 479
persons were treated for chemical poisoning in those years (38). Of this
number, 311 were children and 168 adults. Drugs were by far the most
common cause of poisoning in both children and adults. Aspirin accounted
for 27 percent of all the cases in children. Four persons died from in-
gestion of chemicals—one child from cyanide and three adults from cyanide,
strychnine, and alcohol.
An attempt was made to study the prevalence and characteristics of acci-
dental poisoning in an urban population in Syracuse, N.Y. (52, 55) The
authors obtained their data by direct interviews with a 2 percent sample
of the total population of this city. Thus, 1,069 families with 4,069
members were selected. This group was considered to be reasonable repre-
sentative of the total city population in age, sex, and socioeconomic
status.
A total of 107 poisoning episodes were recorded among the study popula-
tion. Medicines accounted for 63 of the poisonings, 33 of which involved
aspirin. The remaining ingestions - 44 - were due to household products,
petroleum-based chemicals, pesticides, paint and paint products, cos-
metics, and other agents. Physicians were consulted in only 79 of the
total cases. Some of the persons interviewed were not aware of the
hazards of aspirin, and only about 66 percent of these ingestions were
brought to the attention of a physician. This contrasted with the ex-
perience in other types of poisonings where 80 percent or more had sought
medical assistance. The authors were not able to demonstrate any geo-
graphic of socioeconomic aggregation of cases.
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M. A. Heasman presented morbidity data from England and Wales for 1958
and mortality data for the period 1954-1958 (29). The 1958 morbidity
data were obtained from a 10 percent sample of all patients discharged
from the National Health Service hospitals (excluding mental hospitals).
From these records, 1,000 consecutive cases of poisoning were extracted.
A total of 218 of these cases occurred in children under 15 years of age,
about 50 percent of which involved the ingestion of pills, tablets, and
other medicinal substances. In this category, aspirin accounted for 44
of the cases; barbiturates, 28; and other substances, 33. Turpentine,
paraffin, and disinfectants ranked highest among the household products
group, with 18, 16, and 7 cases, respectively. Berries and plant sub-
stances were responsible for 8 cases. Although there were no deaths
among these cases, fatalities in this age group in England and Wales
during the period 1954-1958 averaged 44 per year. As with the hospital
admissions, aspirin and salicylates were the most common causes of death.
Iron preparations were responsible for 12 deaths, and 10 deaths were
attributed to strychnine.
Attention has been focused on the role of pesticides as causative agents
in poisonings (10, 18, 22, 28). The extent of injury from pesticides on
a nationwide scale is difficult to determine, but California publishes a
detailed tabulation of nonfatal injuries from economic poisons annually
(18). The difficulty in compiling reliable pesticide poisoning statis-
tics has been due to the lack of uniformity in identifying and recording
agents responsible for injury. For instance, from a total of 446 entries
listed under the category of poisoning in the International Statistical
Classification of Diseases, Injuries and Causes of Death, only 17 items
relate to pesticides. There are, however, over 400 basic pesticide
chemicals and approximately 45,000 formulations now available. In a
study of pesticide mortality, it was shown that 196 deaths were reported
in 1946, 154 in 1949, 152 in 1950, 132 in 1952, 133 in 1953, 105 in 1954,
and 140 in 1955 (18).
Data submitted by various reporting groups such as industrial commissions
and Poison Control Centers support the conclusion that only the more
familiar materials used as pesticides are included in this category. A
later report (10) included data on mortality from pesticides for the
years 1956 to 1960. Pesticides were reported as the cause of death in
141 cases in 1956, 111 cases in 1958, 130 cases in 1959, and 103 cases in
1960. A paper published in 1964 (28) speculated that the rate of acci-
dental deaths from pesticides was about one per million persons each year.
It was further indicated that there had been no significant change in the
death rate associated with the increased use of the new pesticides.
Results of detailed investigations conducted in certain high pesticide-
use areas of the United States, however, showed a higher death rate. For
example, in Dade County, Florida, which has a population of 1,040,000, 89
deaths due to pesticide ingestions were reported from 1956 to 1964. This
statistic included 23 cases designated as accidental, 52 suicides, and 4
homicides. Parathion, an insecticide not specifically listed in earlier
papers, was shown to be responsible for 9 of 10 deaths among children over
a four-year period (22). A unique problem in Dade County is the illegal
door-to-door sale of parathion in unmarked containers. This activity in
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itself has been shown to be responsible for the deaths of several
children. Data on total poisonings from pesticides reported in three
recent years are shown in Table 1.
TABLE 1
i
REPORTED POISONINGS BY PESTICIDES—UNITED STATES* 1968-1970 '
Pesticide
Insecticides
Rodenticides
Fungicides
Herbicides
Mothballs
Miscellaneous
TOTAL
1968
2,919
1,185
99
254
922
360
5,739
Cases
1969
2,929
1,192
90
281
813
397
5,702
Deaths
1970
2,913
1,132
106
287
933
358
5,729
1968
11
4
0
9
0
0
24
1969
14
6
0
6
0
0
26
1970
13
6
0
1
1
0
21
The etiology of accidental poisoning episodes has been the subject of
considerable investigation. In addition to the more common safety hazards
from improper storage of chemicals, other facets of the problem have been
explored; for example, the role of oral abnormalities. J. 0. Craig (21)
showed that children who poison themselves can be divided into two groups,
those who take the poison (usually in the form of attractive tablets or
liquid), but who only taste or chew the substances and, in the majority
of cases, reject them before harm results; and those who show exaggerated
oral traits, amounting to pica in about 50 percent of the cases, and
poison themselves with tablets of any kind. Tablets attract these chil-
dren more than liquid and candy-flavored tablets such as aspirin or
ferrous sulphate may be ingested in lethal quantities. The risk of death
to children in this group is greater than in the first group.
An attempt was made by Australian workers in 1956 to correlate social
factors with accidental poisonings among children (1). Results of their
study indicated that negligence or carelessness by parents was an un-
common cause of poisoning. In follow-up investigations, the authors found
that 70 percent of the poisoned children came from homes whose parents
were conscientious in caring for their children; 63 percent of the 155
cases were from "standard" homes, and 68 percent of the fathers were pro-
fessional people, businessmen or skilled tradesmen. The smaller number
of children came from poorer families, belonging to the laboring or semi-
skilled groups who had a lower material standard of living.
In other attempts to establish possible social factors in accidental
poisonings, investigations were made of repetitive poisoning cases. One
of these investigations (53) was based on the study of a group of 100
children who had experienced one episode of accidental poisoning. A
group of matched controls was selected from a previous randomized
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population derived from the city of Syracuse (55). The poisoned group
was found to experience many more subsequent episodes of poisoning than
the control group. These children were more active and mischievous, were
more likely to experience falls, and were more frequently separated from
their parents. The girls in the repeater group were described as being
more boyish, and both sexes walked earlier than members of the control
group.
In a later study of the families of 20 poison repeaters, 19 single in-
gesters, and 13 controls, no correlation was apparent between repeated
episodes of poisoning in children, and religious affiliation, income,
geographic setting, or family size (48). Contrary to the study reported
by Wehrle et_ jal. (53), these investigations showed no relationship
between repetitive poisonings and accident proneness, pica, environmental
hazards, or lack of parental supervision. The ingestion of poisons
seemed to be the result of purposeful behavior on the part of the child.
Possible causes of the first ingestion were considered to be the .result
of the child's negativism, imitation of the parent's pill takingj or con-
fusion with food. Subsequent inges^ons were described as methods to get
attention.
Baltimore and Meyer (6) suggested that improper storage and parental
ignorance of toxicity were secondary environmental factors in accidental
poisonings, although no statistical difference in poisoning incidents
could be proved. A statistically significant relationship was found,
however, between "pica" and "daredevilness" in children and poisoning
accidents.
Scientific literature contains a variety of published reports on methods
and programs for the prevention of accidental poisonings. The most
successful program for reducing child deaths was the network of Poison
Control Centers. Their influence on accidents is more difficult to de-
termine since the Centers are not located in all urban and rural areas
and are operated on a voluntary-reporting basis.
Other proposals for the prevention of poisoning incidents have related to
labeling of containers for chemicals (19, 39). The need for precautionary
labeling of chemical products was first formally expressed by the American
Medical Association in 1884 with the adoption of a resolution urging Con-
gress and state legislatures to enact laws requiring containers of lye to
bear a poison label (19). Specific warning statements are required on
various types of products under the Federal Food, Drug, and Cosmetic Act,
the Caustic Poison Act, and the Federal Insecticide, Fungicide, and Ro-
denticide Act (18). The influence of labeling in decreasing accidental
poisoning among children is difficult to assess, however.
A study, made to determine the degree of "attractiveness" of certain medi-
cants, particularly aspirin, to children, indicated that bright colored
tablets were the most popular, with magenta ranking first (37). Brown
placed high among the study population, presumably because of its similar-
ity to chocolate. Wine- and black-colored tablets were low on the list;
therefore, the researcher proposed that aspirin and other drugs be in-
corporated in black-colored tablets and that tablets be dispensed in
plastic strips which are difficult for children to tear.
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In a study reported in 1959 (4), the use of safety closure caps on drug
containers was proposed. Fourteen different types of safety caps were
investigated over a period of three years, and two caps were finally
selected for comparison with the conventional screw cap in a test area
of 1,600 homes that had children under 5 years of age. Over 93 percent
of the children in the survey had difficulty in removing the two experi-
mental caps, and it was concluded that a safety cap was an important and
practical safety measure. In a study in the Tacoma, Washington area (46)
the author found that, after the introduction of bottle closure devices,
the rate of accidental poisonings from tablets dropped from one per 5,100
prescriptions to one per 62,300 prescriptions. Poisonings due to chil-
dren's flavored aspirin were reduced by 97 percent. Similar results were
reported from a Canadian investigation.
In a detailed study of the etiology of a group of 100 poisoning incidents,
Jensen and Wilson (36) found three circumstances, singly or in combina-
tion, that were common to 86 of the cases. In 26 cases, a person other
than the parents (siblings, other children, neighbors, relatives, friends)
played an important part in the episode. These individuals either made it
possible for the poisoned child to reach the substance or failed to prop-
erly store the chemical. In 31 cases the parents were not aware that the
child could climb, open doors, unscrew caps, or perform other tasks nec-
essary to obtain the agent. In 53 cases, the poison was not in its usual
location, either because it was in use, because persons other than the
parents had left it out, or because the parents themselves were careless.
Studies have shown that many accidents could be avoided if parents would
refrain from taking medicines in the presence of their children (9). A
detailed study in the Norwalk, Connecticut area supported the findings
that children will imitate their parents in this respect. It was shown
that of the children poisoned by medication other than aspirin, 67 percent
frequently observed their parents taking pills. This was found in only 13
percent of a comparison group who ingested "baby" aspirin. The investiga-
tor suggested that this factor in poisoning incidents could be minimized
by proper parent education (40). Application of the traditional approach-
es to public health education has been suggested to reduce accidents from
chemicals (54). Included among the educational techniques which have been
employed are films, exhibits, lectures, demonstrations, and the establish-
ment of poison prevention programs with community health councils, Parent-
Teacher Associations, 4-H Clubs, and similar organizations.
A study conducted in Charleston, South Carolina, in 1962 and 1965 (42),
demonstrated the practicality of a concentrated, community-wide program
to reduce the incidence and severity of accidental poisonings. This
survey pointed out that lack of awareness by adults still exists at all
socioeconomic levels. One of the newest approaches to poison prevention
is Poison Central (41) established in Kentucky in 1962, which provides a
master toxicology information and service facility for the state system
of regional poison information and treatment centers. Poison Central
operates on a 24-hour basis seven days a week and provides toxicologic
services not available at regional centers or at local hospitals and
clinics. It also provides readily available services for areas not served
by Poison Control Centers.
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The deliberate ingestion of chemical agents or the so-called "therapeutic
misadventures" or self-poisoning episodes, with or without suicidal in-
tent, is a problem of great concern. This problem, particularly among
young individuals, was noted in New York City after the Poison Control
Center was set up in 1955 (33). The author of a paper on this subject
in the New York area indicated that 299 suicidal attempts by poisoning
were reported for individuals under 20 years old. These episodes took
place between March, 1955, and December, 1958. Females accounted for
232 cases or 78 percent of the total. Puerto Ricans, who compose 11.8
percent of New York City's population, accounted for 28 percent of the
attempted suicides. The primary agents involved were aspirin (84 cases—
28 percent), barbiturates (47 cases—16 percent) and tranquilizers (36
cases—12 percent); the remaining cases were attributed to bleach,
iodine, lye, insecticides, and other chemicals. A definite seasonal
pattern was noted, with the incidence lowest in autumn and highest in
spring. The type of agents used in the New York City cases have been
implicated in similar episodes elsewhere (14).
James Toolan speculated on some of the predisposing causes to suicide
(51). In his report, he discussed two cases involving the ingestion of
chemicals. One of these was a 14-year-old male who swallowed an uniden-
tified toxic agent to prove that he was invulnerable. Another was a
12-year-old girl who attempted suicide by taking a large amount of seda-
tives, because she dreamed of her dead mother and wanted to join her.
The hazards to health from the availability of proprietary drugs like
scopolamine have been a matter of concern because of the involvement of
these chemicals in self-poisoning incidents. This chemical has been the
subject of many reports, including one from Casper, Wyoming (7) where
six cases involving suicidal ingestions were treated in a six-month
period. The authors of that report take exception to advertisements that
emphasize the "safe" or "harmless" character of sedatives containing this
chemical. Other investigators (16) have held similar views concerning
this agent. The toxic dose is reported to be about 3 to 5 mg (12 to 20
tablets).
From the experience of these researchers, self-induced drug intoxications
usually involve five main classes of agents—barbiturates, salicylates,
glutethimide, meprobamate, and phenothiazines. Their experience also
indicated that ethylene glycol, bromides, and scopolamine preparations
are frequently ingested with suicidal intent.
A study dealing with the various aspects of self-poisoning in the Chicago-
Cook County area showed that in 1964, 468 persons were treated for delib-
erate poisonings in the adult emergency department at Cook County Hospital
(30). The preponderance of persons in the group were females (333—71
percent). Persons less than 45 years of age made up 84 percent of the
group; more than half of these were less than 25 years old and a large
number were teenagers. The patients ingested 102 different drugs and
chemicals. Barbiturates were again the agent of choice, followed by the
salicylates and tranquilizers. Rubbing alcohol, bleach, antiseptics, and
rodenticides were also used as self-destructive agents.
,.s 101
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Two comprehensive studies on self-poisoning episodes have been published
by the British in recent years (23, 26). In the Oxford area, it was
shown that 502 females and 200 males, ranging in age from 11 to 85 years,
were admitted for treatment of self-induced poisonings between 1962 and
1965. Females outnumbered males in all age groups. The authors reported
that there were 40 double admissions, seven triple, two quadruple, and
one sextuple. The main poisons used were barbiturates (45 percent of the
cases) and aspirin (26 percent). The use of barbiturates rose steadily
with age from 23 percent in the age group under 20 to 60 percent in per-
sons aged 50 and older. Over the same age span, the use of aspirin
declined from 49 to 12 percent. The highest rate of self-poisonings was
observed among married females under the age of 20. Unmarried girls in
the same age bracket had a lower rate, which was statistically signifi-r
cant. Married women showed slightly higher rates than single women at
all other ages, but both groups showed diminishing rates above the age of
25.. Of the total number of persons in the study population, eight deaths
were recorded (23).
In the Cardiff, Wales, area, all cases of intentional poisoning admitted
for treatment between the years 1950 and 1965 were studied (26). During
this period 1,736 deliberate poisoning episodes (classified as "serious
attempt," "gesture," and "doubtful") were recorded, involving 1,541
patients. The number of female patients (1,048) was greater than the
number of men patients (493) in all age groups, but the greatest number
for both men and women was in the age group 25 to 45; these numbered 199
and 436, respectively. The next highest age group for women was 0 to 25
years and, for men, 45 to 65 years. Multiple admissions occurred in 14
percent of the serious attempts, 7 percent of the gestures, and 11 per-
cent of the group classified as doubtful. Attempts were made to associate
significant organic illnesses with the poisoning gesture. Twenty percent
of the individuals did have some illness at the time of the episode.
Twenty-six percent of the patients had been under psychiatric care, and
38 percent were known to have been suffering a mental illness of one kind
or another, mainly depression before the episode. The agents used in
these incidents were barbiturates, salicylates, and coal gas (carbon
monoxide), which together accounted for 70 percent of the attempts. The
number of fatalities that resulted from the ingestion of these and other
agents was not specified.
The preference of barbiturates over other methods of committing suicide
was. pointed out in a report of an intercultural study of the suicide
problem in Los Angeles, California, and Vienna, Austria. In one recent
year, barbiturates and other drugs and chemicals were responsible for 30
deaths in Los Angeles and 31 in Vienna. The use of chemicals ranked
after domestic gas and hanging in Vienna and shooting in Los Angeles.
The incidence of suicidal attempts (non-fatal) is difficult to establish.
In a study by Parkin and Stengel (44) to determine the incidence of
suicidal attempts in Sheffield, England, for the years 1960 and 1961, the
following definition was adopted: "A suicidal attempt is an act of self-
damage undertaken with the apparent intention of self-destruction,
however half-hearted and ineffective." Results of their study showed
that there were a total of 358 suicidal attempts admitted to hospitals
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in 1960 as compared to 39 actual suicides; in 1961, attempted suicides
treated in hospitals totalled 359 as compared to 47 actual suicides. For
1960, 45 percent of the attempted suicides were attributed to narcotics,
15 percent to salicylates, and 20 percent to other chemical agents; for
1961, 40 percent were attributed to narcotics, 16 percent to salicylates,
and 22 percent to other chemical agents. The remaining attempts for both
years were due to hanging, slashing of the wrists, and other means. •
The prevention of deliberate poisonings involves the application of nu-
merous techniques such as proper counseling of persons with psychological
problems and maintenance of proper controls over drug items. Persons ill
from an overdose of a toxic chemical must receive proper diagnosis and
treatment, and surveillance should be maintained over individuals in high-
risk categories.
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133.
19. Conley, p. E. 1958, Principles for precautionary labeling of
hazardous chemicals, J.A.M.A. 166:2154^2157.
20. Craig, J. 0,, and Fraser, M. S. 1953. Accidental poispning in
childhood. Archives of Disease in Childhood 28:259^267.
21. Craig, J. 0. 1965. Oral factors in accidental poisoning. Archives
of Disease in Childhood 30:419^423.
22. Davies, J. E., Welke, J. 0, and Radomski, J. L. 1965. Epidemiologic
aspects of the use of pesticides in the south. J. Occupational Med.
7(12):612-617.
23. Evans, J, G. 1967. Deliberate self-poisoning in the Oxford area,
British J. Preventive Social Med. 21:97-407.
24. Farberow, N. L. and Simon, M. D. 1969. Suicides in Los Angeles and
Vienna—an interculturaf study of twp cities. Public Health Reports
84(5):389r-403.
25. Fleming, A. S. 1960. Accidental poisoning. Public Health Reports
75:1.
26. Graham, J. D. P. and Hitchens, R. A. N. 1967. Acute poisoning and
its prevention. British J. Preventive Social Med. 21:108-114.
27. Greenburg, L, A. 1950. An evaluation of reported poisonings by
acetylsalicylic acid. New England J. Med. 243:124-129.
28. Hayes, W. J. 1964. Occurrence of poisoning by pesticides. Archives
of Environmental Health 9:621^625.
29. Heasman, M. A. 1961. Accidental ppisoning in children. Archives of
Disabled Children 18:126-133.
30. Hyman, S., and Greengard, J. 1967. Self-poisoning and accidental
poisoning. Postgraduate Medicine 6:578-584,
31. Ingalles, T. H., Tiboni, E. A., and Werrin, M. 1961. Lead poisoning
in Philadelphia, 1955-1960. Archives of Environmental Health 3:575-^
579.
32. Jacobziner, H. 1956' Accidental chemical poisonings in children.
J.A.M.A. 162:454-459,
104
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33. Jacpbziner, H. I960. Attempted suicides in children. Pediatrics
56(4):519-525.. " '',', •
34. Jacobziner, H'J ahd:Raybin, H. W. 1956. Accidental poisonings in
childhood and their prevention. Pediatrics 49:592-606.
35. Jacobziner, H. and Raybin, H. W. 1961. Briefs on accidental chemi-
cal poisonings in Nes York City. N.Y. State Med. J. 61:3893-3900.
36. Jensen, G. D. and Wilson, W. W. 1960. Preventive implications of a
study of 100 poisonings in children. Pediatrics 25:490-495.
37. Jolly, J. and Forrest, T. R. W, 1958. Accidental poisoning in
childhood, an experimental approach to the prevention of poisoning
by tablets. Lancet 1:1308-1309;^
38. Kelley, V. C. and Done, A. K. 1956. Poisonings in childhood. Rocky
Mountain Med. J. 3:291-295.
39. Kerlan, I. 1957. Health problems occurring from household chemicals
including drugs. J.A.M.A. 163:124-1257.
40. Koumans, A. J. R. 1960. A new aspect of accidental poisoning in
childhood. Pediatrics 25:1067-1070.
41. Luckens, M. U. 1968. Poison central: an integrative approach to
poison control. Am. J. Public Health 58(12):2291.
42. Maisel, G., Langdoc, B. A., Jenkins, M. Q., and Aycock, E. K. Anal-
ysis of two surveys evaluating a project to reduce accidental poi-
soning among children. Public Health Reports 82(6):555.
43. Mellins, R. B., Christian, J. R., and Bundesen, H. N. 1956. The
natural history of poisoning in childhood. Pediatrics 17:314-325.
44. Parkin, D., and Stengel, E. 1965. Incidence of suicidal attempts
in an urban community. British Med. J. 2:133-137.
45. Schucker, G. W., Vail, E. H., Kelley, E. B., and Kaplan, E. 1965.
Prevention of lead-paint poisoning among Baltimore children. Public
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46. Scherz, R. G. 1968. Childhood drug poisonings reduced. J.A.M.A.
206(7):1428.
47. Smith, E. J., Lewis, B. W., and Wilson, H. S. 1952. Lead poisoning,
a case finding program. Am. J. Public Health 42:417-421.
48. Sobel, R., and Margolis, J. A. 1965. Repetitive poisoning in chil-
dren: a psychosocial study. Pediatrics 35:641-650.
49. Sunshine, I. Epidemiology of poisoning. Paper presented at the
training course "Principles of Epidemiology" in Atlanta, Georgia, at
the National Communicable Disease Center, November, 1967.
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52. Wehr^e, P. F., Dary, P. A., Whalen, J. P., Fitzgerald, J. W., and
Harris, V. G. I960. The epidemiology of accidental poisoning in
an urban population: prevalence and distribution of poisoning.
Am. J. Public Health 50(12):1925-1933.
53. Wehrle, P. F., DeFeest, L., Penhollow, J.t and Harris, V. G. 1961.
The epidemiology of accidental poisoning in an urban population:
the repeater problem in accidental poisoning. Pediatrics 27:614-619.
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poisoning. Am. J. Public Health 46(6):951-958,
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106
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MONITORING OF ENVIRONMENTAL TOXICANTS
John S. Wiseman
An understanding of the proper techniques for the collection, storage,
and shipment of materials intended for analysis is necessary if envi-
ronmental toxicants are to be accurately monitored. The quality of
the analysis conducted on environmental samples is directly related
to the collection procedure. Although the methodology discussed in
this paper uses pesticides as examples, the overall principles apply
to all environmental toxicants which are intended for analytical
purposes. Monitoring of air, water, soil, adipose tissue, and body
fluids will be discussed.
107
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108
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THE ANALYTICAL LABORATORY—A PANEL DISCUSSION
Frederick W. Oehme, William D. Rhoads, Herbert Starr, and John Tessari
A panel discussion covering four areas of laboratory management was
ducted by representatives of independent laboratories. The discussion
centered around the following topics:
Quality Control. Quality control is used to assure the output of reliable
and valid analytical data. There are basically two general types of
quality control: interlaboratory and intralaboratory. The former term
indicates the involvement of two or more laboratories, providing a
mathematical basis for the confidence placed in the results of sample
analysis and an insight into analytical areas needing attention. An
intralaboratory program provides a systematic system of methodology, use
of standards, clean-up and related procedures within a laboratory to
insure accurate analyses by each analyst. Each panel member discussed
how his laboratory copes with each of these two general types of quality
control.
Confirmation. The nature of analyses is such that interfering materials
and artifacts are often observed and metabolic and decomposition products
may also occur. Low concentrations of chemicals must be detected, meas-
ured, correctly identified, and confirmed by at least two independent
analytical methods. Some methods, such as thin layer chromatography,
paper chromatography, or p-values share the same physical property of
partition in achieving separations of mixtures. They do not give inde-
pendent evidence for the identity of a compound. Gas-liquid chromatography
(GLC) retention times for a compound on different stationary phases are
often highly correlated. Thus, the choice of confirmatory techniques
should be carefully made.
General Problems. Laboratories involved in chemical analysis have their
own unique types of problems. For example, a laboratory has the problem
of separating polychlorinated biphenyls from chlorinated pesticides.
Related problems may include sample collection techniques, storage of
samples, transport and clean-up procedures.
Instrumentation. A variety of scientific instrumentation is being used
today to obtain analytical data. Each panel member discussed the ana-
lytical instruments being used by his laboratory.
109
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11°
-------
POLYCHLORINATED BIPHENYLS IN SILAGE AND HUMAN MILK IN RURAL COLORADO
E. P. Savage, J. D. Tessari, J. W. Malberg, H. W. Wheeler, and J. R. Bagby
In 1966, Jensen first reported residues of polychlorinated biphenyls
(PCB's) in tissues of fish and birds (1). Since then, PCB's have been
identified in a number of different substrates, and the Food and Drug
Administration has reported them in fresh fruits, vegetables, fish,
poultry, eggs, milk, and in other food commodities (2-11). PCB's have
also been reported in human adipose tissue and in human milk. Risebrough
e£ al^. reported PCB's in 16 human milk samples collected in California
(12). Dyment £t jd., in a study conducted in Texas, were unable to find
PCB's in human milk samples from New Guinea and Texas (13). Skrentny
JlJi 2-L' (8) na
-------
OV-1). Solid support material was Chromosorb W, high performance DMCS
100-120 mesh. Temperatures for the Electron Capture Detectors were 300°C,
injection ports and transfer lines 245°C, Columns 200°C, and Inlet 240°C.
Thin layer chromatography equipment consisted of: 8" x 8" glass plates,
8^ x 4% x 8% developing tank, desaga/brinkmann standard counting board,
desaga/brinkmann standard model applicator, spotting pipettes, glass
desicator, and ultra violet light.
t
The extraction procedure used was a modification of those described by
Giuffrida et^ ai^. (14) and Curley and Kimbrough (15) and consisted of three
parts: 1) the fat was isolated from the milk, 2) the PCB's were extracted:
from the fat, and 3) the extract was cleaned up. In our modification,
samples of 15 grams of mothers' milk were placed into clean glass centri-
fuge bottles. Approximately 1 gram of glass wool was added to each
sample. The purpose of the glass wool was to adhere to the coarse
precipitate of the milk solids. After addition of 100 ml. of acetone,
the milk samples were shaken for two minutes and centrifuged at 1000 rpm
for 2 minutes. The acetone layer was then decanted into a one liter
separatory funnel. After decanting, a volume of 25 ml of acetone was
added to each sample and the extraction procedure was repeated three
more times. AH four extractions were then transferred into a liter
separatory funnel. The portion of the milk sample that was coagulated
was then extracted with 2-25 ml portions of n-hexane and centrifuged for
2 minutes at 1000 rpm. The two portions were then transferred into the
one liter separatory funnel and 50 ml n-hexane, and 125 ml of a 2%
sodium sulfate solution was added to the funnel. The separatory funnel
was shaken manually for 2 minutes. The layers were then allowed to
separate and the lower acetone-aqueous layer was drawn off and discarded.
Another 125 ml of 2% sodium sulfate solution was added to the separatory
funnel, shaken manually and allowed to separate. The lower aqueous layer
was again discarded and the upper layer was poured into a 500 ml concen-
trator flask. The solvent flask was transferred to a rotary evaporator
and the solvent extract was removed under water aspirator suction at
37°C until the solvent volume was reduced to approximately 2 ml. The
sample extract was then taken through the Florisil procedure as described
in the Manual of Analytical Methods (16).
The samples were analyzed by gas liquid chromatography. These analyses
were followed by the TLC procedure for PCB's as prescribed in the Manual
of Analytical Methods (16). The silage samples were analyzed by using
the same methods.
Results
The epidemiological data for the eight participants with milk samples
positive for PCB's are shown in Table 1. The levels of PCB's ranged
from a low of less than 0.04 ppm to a high of 0.1 ppm. The range of age
of the positive mothers was from 19 to 26 years. Three were born in
Colorado, one each in Germany, Japan, Michigan, Ohio, and North Dakota.
Seven were Caucasian and one Oriental. Five had lived in a city of
50,000 population or greater at some time during their lifetimes and
three had not. Seven of the women were housewives, and pne was a
secretary. It is of interest that the two highest levels of PCB's were
found in two housewives who had never lived outside of Colorado.
112
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TABLE 1
Epidemiological Date for, Lactatlng Mothers Positive for PCB Residues
Colorado - 1972
Age
25
20
26
22
19
25
20
23
Birth
place
Colorado
Colorado
Michigan
Germany
N. Dakota
Ohio
Colorado
Japan
Occupation
Housewife
Housewife
Housewife
Housewife
Housewife
Secretary
Housewife
Housewife
Race
C
C
C
C
C
C
C
0
i
Lived in
Years lived city larger Levels of
in Colorado than 50,000 PCB's
25
20
3
3
7 months
2
19
1
Yes
No
No
Yes
No
Yes
Yes
Yes
0.1 ppm
0.05 ppm
0.04 ppm
0.04 ppm
0.04 ppm
0.04 ppm
0.04 ppm
0.04 ppm
Of the 31 silags samples originally collected, two were positive for
PCB's. The positive sites were resampled during the summer. Table 2
depicts the positive samples for PCB's collected from the two positive
ranches. Site 20 is a ranch that feeds large numbers of feeder cattlei
Silage is stored in pit silos and one upright silo at this ranch.
TABLE 2
: Silage Samples Positive for PCB's
Weld County, Colorado - 1972
Site No.
20
20
20
21
21
21
21
Collection
Date
5/31/72
8/1/72
9/8/72
5/24/72
8/3/72
8/3/72
9/7/72
Comments
Pit silage - 0,07 ppm
Pit silage - 0.04 ppm
Upright silo - trace
Silage & shelled corn
from cattle trough T
0.06 ppm
Pit silage - 0.08 ppm
Shelled corn - 0.04 ppm
Shelled corn collected
from truck - trace
113
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The silage from Site 20 contained a residue level of 0.07 ppm on the
first sampling and 0.04 ppm on the second sampling. Corn collected from
an upright silo on the same ranch showed only a trace on PCB's and was
at the lower levels of our PCB detection capability.
Site 21 is a dairy operation. The silage collected from the pit silo on
this ranch contained PCB's at a residue level of 0.06 ppm. Collections
of silage and shelled corn taken separately on the second collection had
levels of 0.08 ppm and 0.04 ppm, respectively.
Discussion
Although PCB's were found in silage stored in both pit and upright silos
on Colorado ranches, all of the positive samples were at very low levels,
the highest level being 0.08 ppm. Only two (7.1 percent) of the ranches
sampled were positive. One site had positive samples taken from an
upright and a pit silo. Since this was a dairy ranch, 102 grams of milk
were also collected and analyzed. This sample was negative for PCB's.
The length of time those positive for PCB's had lived in Colorado is of
interest. Seven of the eight had lived in the state a year or longer.
Two had never lived outside of the state and one had lived in another
state for only a year. There were four other study participants who had
never lived outside of Colorado who were negative for PCB's.
This study indicates that PCB's are found at very low levels in human
milk in Colorado. The highest level was 0.1 ppm in a 25 year old house-
wife who has lived her entire life in the state. Six of the positive
samples were at the low level of our detection capability at 0.04 ppm or
less.
References
1. Jensen, S. 1966. New Scientist 32, 612.
2. Holden, A. V. , and K. Marsden. 1967. Nature 216, 1274.
3. Anderson, D. W., J. J. Rickey, R. W. Risebrough, D. F. Hughes, and
R. E. Christensen. 1969. Can. Field Natur. 83, 89.
4. Reynolds, L. M. 1969. Bull. Environ. Contain. Toxicol. 4, 128.
5. Kueman, J. H., M. C. Ten Noever de Braww, and R. H. DeVos. 1969.
Nature 221, 1126.
6. Westoo, G., and N. Koidu. 1970. ACTA Chemica Scandinavica 24, 1639.
7. Duke, T. W., J. I. Lowe, and A. J. Wilson, Jr. 1970. Bull. Environ.
Contain. Toxicol. 5, 171.
8. Skrentny, R. F., R. W. Hemken, and H. W. Dorough. 1971. Bull.
Environ. Contain. Toxicol. 6, 409.
9. Biros, F. J., A. C. Walker, and A. Medbery. 1970. Bull. Environ.
Contam. Toxicol. 5(4), 317-323.
10. Laug, E. P., F. M. Kunse, and C. S. Prickett. 1951. Arch. Industry
Hyg. 3, 245.
114
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11. Quinby, G. E., F. J. Armstrong, and W, F. Durham. 1965. Nature 207,
726.
12. Risebrough, R. W., J. Davis, R. Anastasia, F. A. Beland, and
J. H. Enderson. Submitted to New England Journal of Medicine.
13. Dyraent, P. G., L. M. Hebertson, E. D. Gomes, J. S. Wiseman, and
R. W. Hornabrook. 1971. Bull. Environ. Contain. Toxicol. 6, 532.
14. Giuffrida, L., D. C. Bostwek, N. F. Ives. 1966. Journal of the
A.O.A.C. 49(3), 634-638;
15. Curley, A., and R. Kimbrough. 1969. Arch. Environ. Health 18, 156-
164.
16. Manual of Analytical Methods, Pesticide Community Studies Laborator-
ies Primate Research Center, Perrine, Florida, 1971.
115
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116
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INTERACTION OF PCB'S AND OTHER ORGANOCHLORINES
WITH DUCK HEPATITIS VIRUS
Milton Friend
Introduction
The study of the impact of environmental pollutants on vertebrate popula-
tions has generally been oriented at the direct effects of single compounds,
Thus, we study both the acute (LD5'0) and the chronic (LC5o) toxicity of a
compound, the compound's teratogenic, mutagenic, and carcinogenic poten-
tial, and, in the case of wildlife, its effects on reproduction. As
diverse as these studies are, they provide only limited information on
the hazards of a given compound.
Consider, for example, the variety of food consumed by the average per-
son or wild animal within the relatively short span of a week. Each of
these food items may contain its own particular combination of low levels
of two or more chemical pollutants. The fact that these residues are at
sublethal levels does not necessarily mean that they have no effect on the
host, nor that the effect of combining them can be determined by simply
adding up their relative hazards. I believe that biological interactions
between chemical pollutants, and between these chemicals and various
biological entities such as agents of disease represent the greatest
hazard of many of the environmental pollutants studied to date. This
situation is analogous to an iceberg, with the surface portion represent-
ing such overt, easily studied effects as mortality, and the submerged
portion a variety of biological interactions induced by sublethal levels
of chemical compounds (Figure 1). During the remainder of this paper, I
will consider one of these interactions: that between chemical pollu-
tants and agents of infectious disease.
Overt and
direct effects
Subtle and
indirect effects
Figure 1. Environmental pollution iceberg.
117
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The problem of pesticide-disease interactions has usually been considered
from the viewpoint of disease causing changes in the toxicity threshold
of the pesticide for the host. However, the converse situation, pesti-
cides altering a host's susceptibility to an infectious disease, has
seldom been investigated. Since this is a session on polychlorinated
biphenyls (PCB's) rather than pesticides, I will first describe an exper-
iment combining Aroclor 1254 and duck hepatitis virus (DHV) and then use
data for other chemical compounds to further illustrate this type of
interaction.
Interaction Experiment
Protocol! Tucker and Crabtree (21) reported the minimum acute oral toxic
dose of four different Aroclors to mallards, Anas platyrhynchos, as
greater than 2000 mg/kg of body weight. Studies with other species have
also indicated that Aroclors have relatively low toxicity for birds (13,
18, 19). On this basis, test levels of 25, 50, and 100 ppm of Aroclor
1254 were selected as sublethal levels for mallards and incorporated for
10 days into the diet of 10-day-old ducklings (25 per group); two similar
groups of ducklings received untreated feed (Figure 2). On the llth day
of the experiment, five randomly selected birds from each treatment group
were killed by decapitation and tissues collected for residue analysis
and histology. The remaining birds were placed on untreated rations,
transported about 5 miles to isolation units, and held in preparation for
challenge with DHV.
PCB feed Treatment levels (ppm)
0, 0, 25, 50, 100
Clean feed —
N = 25 for each group
at time 0.
Birds challenged with 1.5
of DHV.
5 birds killed for \. Mortality recorded
residues from each ^^v^ for 80 hour period
treatment group•—V
i
\ I I.I
0 10 15 19
Day
Figure 2. Experimental protocol.
118
-------
On the 15th day of the experiment, all but the "clean" control group were
inoculated intraperitoneally with 1.5 DLD50 of DHV per bird. The inocu-
lum was in the form of a 10 percent liver suspension; the clean controls
received a similar dilution of a DHV-free liver suspension. Mortality
was recorded hourly for the next 80 hours, except between hours 31 to 47
and 62 to 70. All birds that died within the 80-hour experimental period
were necropsied and their brain tissues collected for residue analysis.
After 80 hours, all surviving birds were killed1 and necropsied, and brain
tissue was collected for residue analysis from five randomly selected
birds in each treatment group.
Results. No birds died or showed clinical signs of intoxication during
PCB feeding or during the interim period between PCB feeding and virus
challenge. However, mortality following DHV challenge was significantly
higher at the .01 level of probability (Chi-square = 7.49, 1 df) among
ducklings that had received PCB in their rations (Table 1). No deaths
occurred in the clean control group. The onset of mortality in all PCB-
plus-DHV test groups began at least 8 to 16 hours earlier than in the DHV
controls.
TABLE 1
Mortality among 10-day-old mallard ducklings, fed diets with or
without PCB, following exposure to DHV.
Treatment*
Mortality**
Total
Percent
1st death
Last death
Clean control
DHV control
25 PCB + DHV
50 PCB + DHV
100 PCB + DHV
0/20
3/21
7/20
13/20
8/18"1"1"
0
14
35
65
44
'
62-70
31/47
55
31/47
73
75
76
75
*PCB values in ppm; DHV = 1.5 DLDso/bird.
**0bservations were made hourly except between 31 to 47 and
62 to 70 hours.
..Number of deaths/total sample.
Two birds were lost in a laboratory accident.
All birds that died had gross liver lesions indicative of DHV infection.
No other gross lesions were observed, except for varying amounts of
edema within the pericardium and thoracic cavity of some birds. This
edema was not correlated with either PCB or DHV exposure. No significant
histological changes were observed in sections of heart, liver, spleen,
or brain tissues following PCB feeding. Histological changes in tissues
of birds that died were indicative of DHV infections.
Residue analyses after 10 days of PCB feeding showed that mean brain
residues in control birds were higher than in the 25 ppm test group (133
119
-------
vs. 110 ppm) but lower than in the remaining test groups (Table 2). The
source of this residue in control birds is unknown, but it was not the
ration fed. Analysis disclosed less than 1 ppm (dry weight basis) of PCB
in the control feed. Total residues in brain and liver increased with
the level of PCB in the diet. The ratio of PCB in the brain to that in
the liver was 1.03 for control ducklings and ranged from 0.37 to 0.89 for
those receiving PCB rations.
TABLE 2
PCB residues in rations and tissues of mallard ducklings follow-
ing 10 days of PCB feeding.
Tissue
Treatment Feed*
Brain Liver Liver plus Brain
Clean control
25 ppm PCB
50 ppm PCB
100 ppm PCB
0.62
27.88
67.14
105.90
133
110
196
205
129
241
220
557
262
351
415
762
* Residues on a dry-weight basis.
+ Residues in ppm/gram of fat; all tissue assays represent pooled
samples of 5 birds each.
PCB brain residues among birds that died following DHV challenge, with
one exception, were higher than in birds killed at the end of the ex-
periment (Table 3). The greatest brain residues of PCB were found in
the birds that died the earliest after DHV challenge.
Discussion. The results of this study indicate that a PCB (Aroclor 1254)
at relatively low levels in the diet (25 to 100 ppm) may increase the
susceptibility of mallard ducklings to DHV. None of the levels of PCB
fed resulted in detectable chemical intoxication, even with the physical
stresses of weighing, handling, confinement, crowding during transporta-
tion, transportation itself, and relocation in a different environment.
However, when the stress of an infectious agent was imposed on the birds
five days later, there were two- to four-fold increases in mortality (14%
among virus controls vs. 35% to 65% among PCB •+ DHV test groups), along
with a reduced incubation period for the virus.
This type of response is somewhat alarming when one considers the variety
of free-ranging wildlife exposed to PCB's. A survey of the literature
through 1970 revealed 120 species in which PCB residues had been detected.
Of these, 73 species were birds (Table 4). Similar increase in mortality
was observed when DDT and dieldrin were used instead of Aroclor 1254 in
interaction studies with DHV. In one experiment, mortality among virus
controls was 7% and for ducklings pretreated with DDT or dieldrin,
mortality increased to 47% and 57%, respectively (7).
120
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TABLE 3
PCB residues in the brains of mallard ducklings following
DHV challenge.
Time of Sample (Hours)
ireatment-
Clean control
DHV control
25 PCB + DHV
50 PCB + DHV
100 PCB + DHV
48**
293(2)
.504(1)
48-70**
78(3)
255(2)
204(7)
226(3)
71-80**
286(3)
128(6)
148(5)
80+
60
59
139
88
163
* PCB values in ppm; DHV =1.5 DLD50/bird.
** Pooled samples from birds that died; figure in parentheses
indicates sample size.
+ Pooled samples from birds killed at end of experiment; N = 5
for each sample.
The mechanism responsible for this synergism between DHV and the 3 orga-
nochlorines studied is unknown. An apparent synergistic response
resulting in deaths of rats after exposure to both chlorinated diphenyl
and carbon tetrachloride was reported 35 years ago (4). Since carbon
tetrachloride, like PCB and DHV, is capable of producing acute toxic
changes in the liver (20), these findings suggest that the liver is
involved in the synergistic responses reported. Studies with rats and
other laboratory mammals have disclosed persistent liver lesions follow-
ing PCB exposure. These lesions consist primarily of fat droplets
generally scattered throughout the lobule, atrophy, necrosis of liver
cells, and central fatty degeneration (11, 17). The lack of definite
histopathology due to PCB in the present study may be a result of species
differences, low dosage levels, a relatively short feeding period, or
some combination of these factors. Some birds showed swelling of hepatic
cells, loss of cell nuclei, some inflammatory response, and what appeared
to be fat droplets, but treatment groups could not be distinguished from
each other or control groups on this basis.
Certain diseases, such as obstructive jaundice, untreated alloxan-induced
diabetes, hepatic tumors, and partial hepatectomy, because of their known
effect on the activity of liver microsomal enzymes, might be expected to
interact with pesticides (5). Conversely, since most toxicants are
detoxified in the liver, they might influence the course of a disease
involving agents or conditions that affect the liver tissue. DHV is such
an agent, and in the presence of certain pollutants, apparently interacts
with them to the detriment of the host.
Other evidence for increased host susceptibility to disease following
pesticide exposure can be found in the literature. For example,
121
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Wassermann et al. (22) found significant reductions in antibody production
among rats fed DDT, and Gabliks and Friedman (9) found increased suscep-
tibility of insecticide-treated cell cultures to polio virus, presumably
as a result of inhibition of interferon activity.
TABLE 4
A tabulation of wildlife species with PCB residues
(through 1970).
Classification No. of Species
Birds 73
Fish
Saltwater 32
Freshwater 5
Shellfish 4
Mammals
Marine 5
Terrestrial 1
Total 120
Literature reports of possible pesticide involvement in wildlife disease
outbreaks are more numerous for fish than for warm-blooded species.
Allison et al. (1) concluded that DDT increased mortality in cutthroat
trout (Salmo clarkii) during toxicity trials by reducing resistance to
disease. Schoenthal (cited by Cope (5)) observed a higher prevalence of
furunculosis and fungus disease in DDT-treated salmonids than in control
fish and Lowe (16) found brain parasitism in Sevin exposed spot (Lei-
ostomus xanthurus). but not in control fish. According to studies at
the Fisheries Research Institute at Vodnany, Czechoslovakia, organic
pollution promotes infectious dropsy, ulcers, and furunculosis in fish,
while pollution of inorganic origin can result in blindness, increased
intestinal parasitism, and sexual sterility (2).
Gilbert (10) concluded that mink (Mustela vision) that died of Chastik's
paralysis in his study, were stressed by DDE to the point where they were
more vulnerable to other agents. On the basis of epizootiological data,
Friend and Trainer (8) suggested that epizootics of Type E botulism in
water birds on Lake Michigan and avian cholera in waterfowl, especially
in California and Texas, are field situations where pesticides may be
important factors in the epizootiology of wildlife disease.
Conclusion
Finney (6) has stated that "any attempt to understand fully the toxic
action of a group of insecticides or fungicides must ultimately involve
a study of their behavior when two or more are applied in mixture." Data
presented here emphasizes that interactions of chemicals with other
biological agents must also be studied before we are able to understand
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fully the potential hazards of these chemicals. One need not be a
biologist to appreciate that exposure to environmental pollutants in
nature is continuous and insult from multiple agents (chemical, physical,
and biological) during the life span of an individual is the rule rather
than the exception. Lodge (15) recognized this problem in stating that
while the study of synergism applied to environmental pollution has
scarcely begun, the problems that must be dealt with are alarmingly
advanced.
References Cited
1. Allison, D., B. J. Kallman, 0. B. Cope, and C. Van Valin. 1969.
Some chronic effects of DDT on cutthroat trout. Bur. Sport Fish.
Wildl. Res. Rep. #64. U.S. Government Printing Office, Washington.
2. Anonymous. 1970. Pollution and occurrence of diseases. F.A.O.
Fish Culture Bull. 2 & 3:7. :
3. Cope, 0. B. 1965. Agricultural chemicals and freshwater ecological
systems. In Research in Pesticides, p. 115-127. Ed. C. 0. Chichest-
er, Academic Press, New York.
4. Drinker, C. K., M. F. Warren, and G. A. Bennett. 1937. The problem
of possible systemic effects from certain chlorinated hydrocarbons.
J. Ind. Hyg. Toxicol. 19:283-299.
5. Durham, W. F. 1967. The interaction of pesticides with other
factors. Residue Rev. 18:22-103.
6. Finney, D. J. 1952. Probit Analysis. Cambridge Univ. Press, New
York.
7. Friend, M. 1971. Pesticide-infectious disease interaction studies.
Ph.D. thesis. Univ. Wisconsin, Madison.
8. Friend, M., and D. 0. Trainer. 1970. Some effects of sublethal
levels of insecticides on vertebrates. J. Wildl. Dis. 6:335<-342.
9. Gabliks, J., and L. Friedman. 1969. Effects of insecticides on
mammalian cells and virus infections. Ann. N.Y. Acad. Sci. 160:
254-271.
10. Gilbert, F. F. 1969. Physiological effects of natural DDT residues
and metabolites on ranch mink. J. Wildl. Manage. 33:933-943.
11. Greenburg, L., M. R. Mayers, and A. R. Smith. 1939. The systemic
effects resulting from exposure to certain chlorinated hydrocarbons.
J. Ind. Hyg. Toxicol. 21:29-38.
12. Hanson, L. E. 1958. Histological lesions in ducks with virus
hepatitis. Amer. J. Vet. Res. 19:712-718.
13. Koeman, J. H., TenNoever De Brauw, M. C., and R. H.:DeVos. 1969.
Chlorinated biphenyls in fish, mussels and birds from the River
Rhine and the Netherlands coastal area. Nature 221:1126-1128.
14. Levine, P. P. 1965. Duck virus hepatitis. In Diseases of Poultry,
p. 838-843. Eds. H. E. Blester and L. H. Schwarte, Iowa State Univ.
Press, Ames.
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15. Lodge, J. P., Jr. 1968. Environmental synergisms: the problem
defined. In Environmental Problems, p. 146-159. Ed. B. R. Wilson,
J. B. Lippincott Co., Philadelphia.
16. Lowe, J. I. 1967. Effects of prolonged exposure to Sevin on an '
estuarine fish, Leiostomus xanthurus Lace"pede. Bull. Environ.
Contam. Toxicol. 2:147-155.
17. Miller, J. W. 1944. Pathologic changes in animals exposed to a
commercial chlorinated diphenyl. U.S. Pub. Hlth. Rep. #59:1085-1093.
18. Peakall, D. B., and J. L. Lincer. 1970. Polychlorinated biphenyls:
another long-life widespread chemical. BioScience 20:958^964.
19. Presst, I., D. J. Jefferies, and N. W. Moore. 1970. Polychlorinated
biphenyls in wildbirds in Britain and their avian toxicity. Environ.
Pollut. 1:3-26.
20. Smith, H. A., and T. C. Jones. 1957, Veterinary Pathology. Lea &
Febiger, Philadelphia.
21. Tucker, R. K., and D. G. Crabtree. 1970. Handbook of toxicity of
pesticides to wildlife. Fish Wildl. Serv. Res. Pub. # 84. U.S.
Government Printing Office, Washington, D.C.
22. Wassermann, M., D. Wasserman, Z. Gerhson, and L. Zellermayer. 1969.
Effects of organochlorine insecticides on body defense systems.
Ann. N.Y. Acad. Sci. 160:393-401.
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CARBON MONOXIDE AS A NATIONAL PROBLEM
Richard E. Gallagher
It has been conservatively estimated by public health officials that more
than 10,000 persons per year are overcome or seriously incapacitated due
to exposure to hazardous levels of carbon monoxide gas. More signifi-
cantly, mortality records reveal that an average of 1,400 persons per
year die as a result of carbon monoxide (CO) poisoning.
Analysis of mortality statistics reveals that approximately 70 percent
of all fatal injuries of this type occur in the home environment. It is
also of value to note that more than 50 percent of these injuries occur
during what is commonly known as the heating season.
The reported numbers of deaths and injuries due to CO are believed to be
only the "tip of the iceberg." Public health and medical authorities
believe that many more injuries and deaths occur as a result of carbon
monoxide poisoning but are not reported because CO is not suspected and
may not be recognized. Carbon monoxide victims are often diagnosed and
treated for such varied ailments as food poisoning, influenza, sinusitis,
pneumonia, and typhoid fever, as well as cardiac failure, viral infec-^
tion, meningoencephalitis, acute alcoholism, and mental illness. Accord^
ing to health authorities in one state, a person was admitted to a mental
hospital four times before he was diagnosed as having GO poisoning.
For more than a half century, the occupationally related hazards of car-
bon monoxide have been well known. However, it has only been recently
that injury and death resulting from exposure to hazardous levels of
carbon monoxide have been of concern and accepted as a significant public
health problem.
Our civilization could not exist as we know it without the combustion of
fuels. Carbon monoxide, one by-product of combustion, is increased when
there is incomplete combustion. It comes from our non-nuclear power
plants, from our automobiles, heating appliances, fuel-fired clothes
dryers and kitchen ranges. In reality, varying concentrations of carbon
monoxide continuously surround us.
CO weighs slightly less than air (specific gravity 0.9671), yet it has
been calculated that not less than 102 million tons of this toxic gas
annually dumped into our nation's living, working, and recreational envi-
ronment (7). In commercial and industrial work areas, CO often reaches
levels detrimental to health. One study reported in the Archives of
Industrial Health found the CO level in a large cold storage plant had
reached 400 ppm (5). Another, conducted by Dr. Stephen Ayers, reported
CO in excess of 100 ppm in New York traffic terminals, with occasional
concentrations of 200 ppm (2). A 30-day study conducted in the GSA garage
of a federal building found CO readings as high as 400 ppm for short
periods of time arid an average of over 50 ppm for a 72-hour period (8).
CO is an odorless, tasteless, and colorless killer which combines with
the hemoglobin in our blood, decreasing the capability of the blood to
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carry life-giving oxygen. It does this by combining with the red blood
cells. In fact, the affinity of carbon monoxide for hemoglobin is over
200 times that of oxygen.
To bring our exposure to CO into perspective, reports state that concen-
trations of COHb as low as 5% to 19% have been associated with adverse
health conditions. These conditions are delayed reaction time, impaired
vision, and artherosclerotic changes in the main trunk of the aorta (3,
4,6).
Professor Astrup and his Danish research team reported in the March 1972
issue of Scanorama that "workers in steel mills, traffic tunnels, garages
and some other environments get more than their share of noxious fumes.
It might be that as little as 2% COHb continuously or intermittently for
several hours a day could be harmful. If a large-scale experiment with
200 rabbits proved this, then I think that 2% COHb in man also would have
a harmful effect." (1)
In this study, COHb levels of around 18% (approximately 200 ppm during
gestation) considerably increased the neonatal death rate of rabbits,
especially on the first day of life. The rabbits bore 120 young; only
one rabbit from the unexposed control group was stillborn, whereas 46
from the same size study group were stillborn or died the first day.
Five of the study group were born malformed (with shorter limbs, for
example), a phenomenon that was never seen in previous experiments in
the Danish lab. After 6 days, the death rate was twice as high in the
study group as in the control group. The experiment was repeated with
only 8% COHb blood levels (a level constantly carried by many heavy
smokers), and a similar tendency was noted in the results (1).
Many researchers believe that CO crosses the placenta and replaces
enough vital oxygen in the blood of the fetus to interfere with normal
central nervous system development. When CO affects the central nervous
system, a person is more likely to have an accident while driving, during
recreation, at work, or at home.
The 1971 Report of the Surgeon General on Smoking indicated that women
who smoke or receive low levels of CO continuously or intermittently
for several hours a day from any environmental source tend to have more
complicated pregnancies and produce more premature lightweight babies.
These findings were recently supported by a mother and child survey of
350 women at Yale-New Haven Hospital in Connecticut.
Since injuries and deaths resulting from exposure to unsafe levels of
carbon monoxide in the home are often of the same magnitude as many of
the communicable diseases, it is fitting that public health officials
should concern themselves with this problem, channeling a considerable
amount of their energies and expertise toward dealing with CO poisoning
in a manner similar to that being used in combating communicable diseases.
It is imperative that public health workers recognize at the outset that
epidemiological methods and techniques which will be used in dealing with
the problem of carbon monoxide poisoning at the domestic level must
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involve the study of influences of many kinds, including the character-
istics of a host population, specific agents, and biological, social and
physical environment. Keeping this in mind, I would like to share with
you the experience of one city-county health department in their effort
to combat CO on a community-wide basis.
In 1964-65, the Memphis and Shelby County Health Department conducted a
study of carbon monoxide in homes. The study was based on investigations
of incidents of carbon monoxide exposures obtained from the following
sources:
1. Reports from the emergency rooms of Memphis city hospitals.
2. Complaints of fumes reported to the Memphis Light, Gas,
and Water Company.
3. Random home surveys in selected neighborhoods.
This study revealed that the following factors contribute to unsafe levels
of carbon monoxide gas in the home:
1. Flame impingement on metal surfaces.
2. Clogged air mixing inlets.
3. Poorly designed and/or improperly modified appliances.
4. Failure to vent gas appliances.
5. Leaks in combustion chambers and heat exchangers.
6. Improperly installed and/or clogged vent pipes.
7. Malfunctioning fuel regulator valves.
8. Oxygen depletion and negative pressure situations.
9. Improper use of fuel (charcoal, coke, fuel oil, L.P. Gas,
etc.)
The following recommendations were put forth as a result of this study:
, 1. The installation of all combustion appliances should be
by qualified persons (often these are not available in
small towns resulting in plumbers and "do-it-yourselfers"
doing the installation).
2. Heating systems should be checked and given routine pre-
ventive maintenance at least annually by qualified per^
sons ("qualified" is difficult to define).
3. All combustion heating appliances should be vented to
the outside of the building.
4. Only the fuel designated by the manufacturer should be
used.
• i
5. Only appliances that bear the seal of a recognized
approval agency should be used.
6. Open flame space heaters that are not adequately guard-
ed, vented and equipped with fuel pressure regulators
should not be used in homes.
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7. Provide source of make-up air to avoid the problem of
negative pressure.
Analysis and interpretation of this preliminary study immediately showed
that the staff from the Memphis and Shelby County Health Department was
not large enough to deal with a public health problem of the scope and
magnitude that was identified.
A manpower survey was made by representatives of the Division of Injury
Control to determine if other assistance was available in Memphis and
Shelby County to deal with the problem of carbon monoxide poisoning in
the home. It was determined that there were seventeen other official
and non-official agencies in the city and county which had interest in
the total accidental injury problem similar to that of the Division of
Injury Control.
Each of these agencies was provided with packets of information on carbon
monoxide poisoning. Each was requested to contribute in a manner con-
sistent with its ongoing functions. Also, it was determined that public
service time was available at no cost through all local radio and tele-
vision stations. Even more importantly, the aid of all sanitarians,
public health nurses, and investigators was solicited in developing a
manpower source capable of dealing with the carbon monoxide problem in
Memphis and Shelby County.
One other important element which was extrapolated from this preliminary
study was that there was little, if any, community knowledge about the
total problem of carbon monoxide poisoning in the home. To assure maxi-
mum receptivity and response on the part of other agencies, co-workers,
and the community at large, community information sessions were held for
all interested groups and organizations. An in-depth training session
was provided for all staff members of the health department. This session
sought to maximize the effectiveness of health department representatives
in identifying those situations in the home which are indicative of car-
bon monoxide poisoning by orientating them in the basic principles of
carbon monoxide poisoning.
All representatives from other agencies which were involved in some phase
of accident prevention were invited to a joint meeting. Each listed how
his agency could contribute to the total community effort.
To assure maximum dissemination of community information, selected radio
and television spot announcements using all local voices were recorded
and distributed to all stations.
Since the initiation of this program, the county's death and injury rate
due to CO poisoning has declined despite an increase in population. The
radio, television, and other news media continue to provide public ser-
vice time to support a continuous county-wide CO educational program. CO
poisoning prevention programs are being conducted by many of the seven-
teen original cooperating agencies and coordinated by the local health
departments.
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CO in any community is one element of a total environment, and as such,
may combine with other stressors with a synergistic effect. Exposure to
non-lethal levels of CO in a dwelling or outdoors in the ambient air is
not a desirable condition; however, the situation becomes worse if the
exposed person is at the same time subjected to the additional stresses
that are common in many of our inner city neighborhoods today. These
stresses include crowding, lack of privacy, lead poisoning of children
who eat peeling flakes of lead-based paint, congestion within the neigh-
borhood, lack of accessibility to essential health and medical services
and to recreation areas. In addition to these stresses, a deprived
living environment often includes inadequate lighting, poor ventilation,
excess noise, wide variations in temperature, nauseating odor, poor
sanitation, rats, burn hazards, and a host of other potential environ-
mental and health hazards.--,;,,
11*
We have known about the health hazard associated with CO for many years.
Until 5 or 6 years ago, industrial standards prohibited an individual
from working an 8-hour day in an environment containing more than 100
ppm of carbon monoxide. Increased scientific knowledge has created a
concern for exposure to excess amounts of CO and as a result the indus-
trial standard has been reduced from 100 ppm to 50 ppm for an 8 hour day.
There is some indication that an exposure of 8 or more hours to a CO
concentration of 10 to 15 ppm has been "associated with adverse health
effects as manifested by impaired time interval discrimination." (4) In
other words, with exposure to low levels of CO, your likelihood of having
an accident while driving, at work, during recreation, or even at home,
may be increased.
There are those who question the current industrial standard of 50 ppm.
the H.E.W. publication "Carbon Monoxide—a Bibliography with Abstracts"
(9) indicates that even 10 to 15 ppm over 8-hour periods does the human
organism no good. Duration of exposure to CO gas is definitely a factor.
For this reason we are concerned with the mother and child, the ill and
aged who spend 24 hours each day in a low concentration of CO.
It would appear that a maximum acceptable concentration of CO in dwell-
ings which would result in no adverse effects on the health and well
being of the occupants should be established and enforced. The Bureau
of Community Environmental Management is in the process of selecting an
ad hoc committee of the most prominent scientists and researchers from
the U.S. and Canada to assist us in establishing a maximum permissible
CO level for the home environment. It is hoped that this standard will
be established by the beginning of the 1972-73 heating season. However,
a standard is of little value unless it is applied at the local level.
Now, let us consider some of the essential components of a comprehensive
action program at the State and community level. First of all, such a
program should include a surveillance function. This will keep you in-
formed of where the problems are, who is affected, and new problems that
may be emerging, and will also provide a baseline against which progress
can be measured. Mechanisms can be established that will ensure prompt
notification to the health department of all incidents involving high
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high carboxyhemoglobin levels in people and high CO levels in dwellings.
This can be done through the cooperation of hospitals, fire and police
departments, gas utility companies, coroners' offices, and others. Sur-
veys of homes using CO detection equipment or screening devices should
become a routine part of housing inspections.
The second part of a community action program should be the prompt in-
vestigation and reporting of cases of CO poisoning, fatal and nonfatal.
We should learn all we can about the individuals involved, the emitting
sources, how the problem relates to existing codes or regulations, and
the general environment in which the events take place. This informa-
tion is essential in developing countermeasures and in determining the
direction of an action program. In the case of malfunctioning heating
and cooking appliances, it is important to know the name of the manu-
facturing company, model number, serial number, date of installation,
what maintenance had been provided, and how the installation was accom-
plished. Health and medical histories and other background information
about the individuals involved are important. Identification of all
CO emitting sources, air exchange characteristics, and other stresses
in the environment includes other essential information to be obtained.
This requires a referral system and the cooperation of several community
agencies.
Implementing control measures involves a wide variety of activities.
Codes and ordinances must be adopted, checked, revised if necessary, and
enforced. For example, what does your community require about the sale,
use, and installation of space heaters? Does it require specific peri-
odic inspection of furnaces and chimneys? Are air samples in occupied
dwellings a part of housing inspections? The answers to these questions
must be in the affirmative to effect sound control measures by an action
program.
Education directed at various segments of the community is a must. The
health department staff and housing inspectors are key participants in
the program and must be informed and motivated. The index of suspicion
of medical and paramedical professions of CO poisoning must be elevated
and periodically stimulated. The utility companies must participate.
Plumbers and other contractors need to be informed. Various segments
of the general public must be informed and motivated.
Behavioral scientists tell us that before a person decides to act posi-
tively to protect his health, three conditions or beliefs must be satis-
fied. These beliefs related to CO are 1) that he can be susceptible to
CO poisoning in his home environment, 2) that exposure to the gas could
have serious consequences for him or his family, and 3) that recommended
control measures will be effective. The absence of any one of these
beliefs almost assures that no decision to act will be made.
Educational efforts directed at and involving children can be very
effective. The concept that accidents are caused and are not "acts of
God" can easily become an important part of a youngster's intellectual
development.
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Two community projects that might be considered as part of a broader com-
munity program that contain elements of surveillance, epidemiology, and
implementation of control measures are the following:
1. Local industries, as part of their off-the-job safety
program, could be motivated th use CO detector screening
tabs in the manner described by the Argonne National
Laboratory during its 1969 project. In this project,
workers were informed about potential CO hazards in homes
and automobiles. They were given the opportunity to place
small CO detector tabs (screening devices) in their auto-
mobiles and homes for several days. A short questionnaire
was distributed to be returned by each user with the tabs.
Contacts were made with the persons reporting or returning
darkened tabs (positive CO finding) and, where possible,
the presence and concentrations of CO were evaluated by
sampling with portable CO detector instruments. In the
case of automobiles, testing was conducted in an area
adjacent to the laboratory. Twenty-seven percent of the
individuals participating obtained positive indications of
CO in either their homes or their automobiles. This
project resulted in corrective actions being taken, such
as repairing automobile exhaust systems, replacing home
furnaces, and improving exhaust ventilation on home gas
heaters. It appears that since the CO tabs are generally
reliable as a screening device and relatively inexpensive
(about 50
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community awareness and concern about the/problem. This will be
evidenced by individual and group actions, such as upgrading existing
regulations or establishing new ones.
CO community action programs offer something which seems to be lacking
in many other community health programs. They offer approaches to the
problem which are practical and simple to do. They are easily under-
stood and consequently appreciated by residents. This is especially
true since the hazard has something of an aura of mystery about it—CO
cannot be seen, smelled, tasted, or felt; and it strikes without warn-
ing. Community prevention programs will contribute to improved public
relations for your department and will stimulate the morale of staff
members who will readily see the tangible benefits in preventing ill
health from an obvious environmental stressor.
References Cited
1. Astrup, P. and D. Trolle. March 1972. Hello, carbon monoxide! SAS
Scanorama.
2. Ayers, S. St. Vincent's Hospital, New York. Consultant Conference
NIOSH, 3/28/72.
3. Ayers, S., S. Gianelli, Jr., and H. Mueller. Myocardial and system-
ic responses to carboxyhemoglobin. Ann. N.Y. Acad; Sci., vol. 174.
4. Beard, R. R. and N. Grandstaff. Carbon monoxide exposure and cere^
bral function. Ann. N.Y. Acad. Sci., vol. 174.
5. Bloomfield, B. D. February 1957. Lift trucks raise CO level.
Archives of Industrial Health 15: 172-173.
6. McFarland, R. The effects of exposure to small quantities of CO on
vision. Ann. N.Y. Acad. Sci. 174:301-312.
7. National Air Pollution Control Administration. March 1970. Air
Quality Criteria for Carbon Monoxide.
8. Polk, L. and E. McCabe. BCEM, DCIC, unpublished report, 4/7/72.
9. Public Health Service. Carbon Monoxide: A Bibliography with
Abstracts. P.H.S. Publication # 1503.
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CARBON MONOXIDE POISONINGS AT HIGH ALTITUDES
Freeman D. Fowler
A knowledge of the causes, effects, and treatment of carbon monoxide
poisonings in man has been gained during thirty-six years as a medical
practitioner in the small mountain town of Idaho Springs, Colorado.
Idaho Springs is located in a canyon at an altitude of 7540 feet near
two major highways that cross the Continental Divide. Highway grades in
and near Idaho Springs are very precipitous and one hill near the commun-
ity increases 1500 feet in altitude in a distance of three miles.
Tourists who come to Colorado's high country to escape the heat of their
home communities seem to be the most frequently affected by carbon
monoxide poisoning. They come in short pants and get up on Berthoud
or Loveland Pass where it is cold, so they close the car windows and may
begin to experience the symptoms of carbon monoxide poisoning.
The risk of carbon monoxide poisoning is greater above 7,000 feet alti-
tude than it is at sea level because the lack of sufficient oxygen at
high altitudes results in poor combustion, causing motor vehicles to
emit much more carbon monoxide. At the same time, the human body is
deprived of about half of the blood's normal oxygen carrying capacity,
thus making the body unable to cope successfully with only half as much
carbon monoxide.
Important aspects to be considered in carbon monoxide poisonings are:
the source of carbon monoxide, the effect of weather and barometric
pressure, and other time and place considerations.
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CHEMICALS IN THE WATERS OF THE ROCKY MOUNTAIN REGION
Charles G. Wilber
For those who are not familiar with some of the unique factors associated
with natural waters in the Rocky Mountain region, it is important to re-
alize that there are few rivers, streams, or ponds in the Rocky Mountains
that have not been modified by human endeavors. Streams are rechanneled,
diverted, diluted and otherwise modified—primarily for purposes of
irrigation but also for purposes of domestic water supply. These modi-
fications sometimes are minor; at other times they are of a major nature
with significant consequences. In many instances, the detailed changes,
with respect to time, etc., have not been recorded in such a way as to
permit the scholar to get a clear historical picture of some of these
modifications.
One of the changes which is common is the transmountain diversion of
water. For example, at the end of 1957, an average of about almost
500,000 acre feet and over 37,000 tons of dissolved solids were diverted
annually from the upper Colorado River Basin over to the eastern slope
of the Rocky Mountains. Of these total amounts, over 350,000 acre feet
of water and nearly 18,000 tons of dissolved solids were diverted from
the Colorado River and its tributaries above the Gunnison River. This
area of the river is sometimes referred to as the "Grand River" by so-
called purists.
Such large diversions across the mountains can result in significant
changes in the adjusted average for dissolved solids concentration when
the flow of a stream or a complex of streams is depleted by diverting
significant amounts of water across the Continental Divide:
For example, the transmoutain (sic) diversions from the Colo-
rado River above Hot Sulphur Springs, Colorado, have decreased
the average annual water discharge from about 417,300 acre
feet in 1914 to about 176,800 acre feet in 1957; have de-
creased dissolved-solids discharge from about 34,900 tons to
about 18,260 tons; and have increased the weighted-average
concentration from about 61 to 76 ppm.
Calculations have indicated that the diversion of water eastward across
the mountains has increased the adjusted average concentrations of dis-
solved solids at Lee Ferry, Arizona, by about 3.4 ppm for every 100,000
acre feet of water diverted across the mountains.
It is known that nearly 300 inorganic chemical species may exist in the
fresh water environment. However, a detailed survey of the published
literature indicates that only 87 species of inorganic chemicals have
been identified. A wide distribution of these chemicals in concentra-
tions in drinking water and in polluted water is reported. There are
data available on acute toxicity, chronic toxicity, carcinogenicity,
mutagenicity, and teratogenicity. The design of the vast majority of
reported toxicological experiments is such as to frustrate attempts to
extrapolate this information to problems of human health. In most cases,
the data were collected with reference to the adverse effect of these
.:' 135
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chemical species on aquatic organisms. Man was not Included as a
possible target organism in most of the considerations.
In the literature, there are numerous correlations made of minimal le-
thal dose versus maximum concentrations reported in fresh water, and of
minimum chronic toxic dose versus maximum concentrations reported in
drinking water, etc. However, the method of reporting and the mathe- ;
metical manipulations used do not aid, in a direct and meaningful way,
the expert who is charged with problems of human health. ;
i
It is long overdue that concern for fish, worms, snails, and fly larvae
be moderated and more direct attention be paid to the impact of chemical
species in fresh water, as individual chemicals and as chemical complexes,
on the human organism both acutely and chronically. Admittedly, such an
orientation is extremely difficult to implement but it is essential if we
are to make any progress with respect to environmental pollution problems.
It is important to realize that an assortment of chemicals in unusual
concentrations in water can modify drastically the biology of a species
without directly killing that species. For example, fish are known to
respond physiologically to a combination of sewage pollution and low
levels of dissolved oxygen. The effects that are seen include decreased
swimming stamina and respiratory efficiency. In addition, there is a
decrease in oxygen consumption and an elevated blood and muscle lactate.
Under these conditions, there is a suppression of urine flow and an
increase in the amount of ammonia excreted. The elevated ammonia excre-
tion is especially pronounced in the presence of environmental ammonia.
Careful study indicates that long-term disruption of the normal hemato-
logical picture in the fish and of the lipid metabolism are identified.
Most of the effects are observed at dissolved oxygen concentrations just
below 5 mg/1, with the exception of the synergistic effects between
ammonia and low dissolved oxygen which are observed at somewhat higher
concentrations of dissolved oxygen (6).
When one considers a complex chemical mixture such as fresh natural >
water, the phenomena of synergism and antagonism must be recognized.
A synergist is a chemical agent which by itself may be mildly effective ;
biologically (e.g., non-toxic) but when combined with some other chemical
species results in a greatly increased biological action (e.g., greater
toxicity, more pronounced rate change of a function). The sum of the 3
individual actions of the two chemicals is always less than the action of
the mixture of the synergists. The phenomenon resulting from the action -
of synergists is called synergism, activation, or potentiation (18). !
The phenomenon of synergism is one of great importance in any
biological consideration of water pollution. It is a factor
in evaluating the biological effects of metals polluting natu-
ral waters. Few polluting effluents are solutions of a single
pure chemical; most are complex mixtures which present every
opportunity for interactions such as antagonism and synergism.
Copper and zinc salts are known to have a synergistic action
when tested against some fresh water fishes. Studies using
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the rainbow trout show that the manner in which toxic action
is exerted is similar for zinc and copper.
In low concentrations of a combined mixture of zinc and copper
sulfates, the toxic action of the mixture can be predicted
from the sum of the toxic actions of the individual salts,
that is, an example of "similar joint action."
At high concentrations in soft water, the toxicity of a mix-
ture of copper and zinc sulfates for rainbow trout is greater
than can be predicted from the sum of individual toxicities,
that is, synergism occurs. The levels of concentration of
copper and zinc at which synergism occurs are so high as to
suggest that under reasonable conditions to be expected in
polluted waters, similar joint action will occur; synergism
will be of no practical importance.
Young Atlantic salmon, Salmo salar, are sensitive to copper
and zinc. The incipient lethal level (concentration below
which the experimental fish survive indefinitely) for copper
is 48 yg/1; for zinc, 600 Mg/1. Above the incipient lethal
level, a plot of log concentration of metal against time to
50% mortality gives a straight line for both zinc and copper.
If both zinc and copper are present in a mixture of salts,
young Atlantic salmon die much faster (by a factor of 2) than
one would anticipate from a simple summation of individual
toxicities. Young temperature-acclimated salmon survive a
given concentration of zinc only one-fourth as long at 15 C
as at 5 C. The incipient lethal level for zinc is elevated
about 1.5 times at 5 C.
Is only dissolved zinc toxic, or is zinc in suspension also
toxic to fishes? Studies using rainbow trout as the test
organism suggest that suspended zinc is toxic. Other inves-
tigations using the Atlantic salmon indicate that only
dissolved zinc is toxic. Additional research on this prob-
lem is needed. Answers are required for all metals which
are potential water pollutants to clarify whether suspended,
dissolved, or both forms of an element are toxic. Moreover,
data are required to clarify the role of precipitated metals
in any kind of toxic interaction. Studies at the molecular
level of the mechanism of toxic action of these metals on
aquatic animals should be encouraged.
Antagonism is essentially the opposite of synergism. The total effect
of the individual chemical agents is less than the sum of the separate
effects when taken independently. The mechanism is obscure. Perhaps
it is simply the precipitation of the active species in an insoluble
form.
Industrial effluents contain organic chemicals, inorganic chemicals, or
both. Synergism and antagonism probably are involved in the final overall
biological action of the effluent. The quantitation of these phenomena
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under field conditions (except under special circumstances) is difficult.
Thus, little is known about synergism or antagonism as it occurs in re-
ceiving waters into which industrial effluents flow.
Stream Flow
In order to understand some of the problems associated with studies on
the chemistry of Rocky Mountain waters, one must recognize that the nat-
ural yearly flows vary widely from virtually zero to impressive floods.
Moreover, man has manipulated these running waters in a bewildering
fashion. Flowing waters are dammed, diverted, run into foreign channels,
and otherwise modified to meet the needs of man—primarily agricultural.
The Cache la Poudre River near here is a controlled flow stream whose
waters are bastardized by periodic injections of foreign water as re-
quired for irrigation. These manipulations complicate ones understanding
of the chemical dynamics of Rocky Mountain waters.
The following table illustrates the flow pattern of the Colorado River:
Location
Grand Lake, Colorado
Glenwood Springs, Colo.
Cameo, Colorado
Utah State Line
Mean Discharge
CFS Acre ft/yr
98 70,880
2,812 2,036,000
4,032 2,919,000
6,088 4,40B,000
Extremes, CFS
Max . Min .
1,840 1.6
30,100 286
36,000 700
56,800 960
Another way of illustrating variability of stream flow is through the use
of the average discharge and the standard deviation. The following table
illustrates these facts:
Location
Fraser River
Colorado River
Blue River
Rifle Creek
Parachute Creek
Gunnison River
San Miguel River
Yampa River
Elk River
White River
Little Snake River
Ave. Discharge
CFS
41
676
116
25
30
2,600
374
472
356
638
547
St. Dev.
CFS
12
189
31
4
20
1,040
158
126
91
142
185
Coef. of
Var.
.29
.28
.27
.16
.67
.40
.42
.27
.26
.22
.34
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Uncontrollable factors which face the biologist who is attempting to
evaluate the role of chemicals in Rocky Mountain waters include the fact
that so many of the major streams and rivers in the Rocky Mountain region
have an extremely variable flow. The Colorado River is an example which
may be useful to set the stage. At Glenwood Springs, the average flow of
the Colorado River, for over a 60-year observation period, is 2,812 cubic
feet per second. However, the range is rather remarkable—from a maximum
discharge of over 30,000 cubic feet per second to a minimum of around 286
cubic feet per second. Farther downstream, at Cameo, Colorado, the
average discharge observed between 1933 and 1957 is a little over 4,000
cubic feet per second. The range again is remarkably wide; the maximum
discharge is 36,600 cubic feet per second, the minimum 700 cubic feet per
second. At the Colorado-Utah State Line, the average flow of the Colo-
rado River measured for a short period of time in the 1950*s was over
6,000 cubic feet per second. The extremes went from a maximum discharge
of nearly 57,000 cubic feet per second to a minimum of about 1,000 cubic
feet per second.
Measurements have been made of the Yampa River flow at Steamboat Springs;
over a half century, the average discharge is somewhere around 500 cubic
feet per second. However, the range is from a high value of nearly 7,000
cubic feet per second to a low value of 4 cubic feet per second. Further
downstream at Maybell, the Yampa River (which at that point drains an
area of about 3400 square miles) has a 50-year average discharge of 1,587
cubic feet per second. The maximum discharge recorded is nearly 18,000
cubic feet per second, the minimum 2 cubic feet per second.
With the enormous ranges in stream flow which are characteristic of these
Rocky Mountain rivers, it is obvious that the chemical picture changes
drastically over a normal course of time. In fact, a number of consider-
ations lead to the suggestion that the normal, natural changes in stream
flow are of such a magnitude as to overshadow and virtually engulf any
man-made changes which might result from industrial operations or, indeed,
from reasonable agricultural operations.
In all probability, future manipulations of these rivers by man will be
in the direction of stabilizing, over the course of time, the stream
flow. When the discharge rate varies so extremely, it is evident that
the aquatic organisms are subjected to overwhelming stresses. The fact
that these stresses have occurred for millions of years suggests that
the native organisms have adapted in some way to these regular insults.
However, it also seems important to recognize that for the best possible
multiple, compatible use of these rivers for domestic purposes, for
industrial purposes, for agricultural purposes, and for recreational
purposes, a more stabilized discharge rate seems desirable.
Trace Elements
Heavy metals in United States waters are a matter of widespread concern.
Some of this concern is hardly warranted despite the sound and fury
accompanying it.
Most States in the Union have established acceptable levels for heavy
metals in water where such standards can be arrived at in a rational manner.
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According to the Environmental Protection Agency (5), Colorado has adopt-
ed the following standards:
Metal
Cadmium
Chromium
Lead
Silver
Zinc
Level in mg/ liter
0.01
0.05
0.05
0.05
0.05
Applied to
Water supply
Water supply
Water supply
Water supply
Water supply
Other Rocky Mountain States have established standards as follows:
Metal Level in mg/liter Applied to
Arizona
No specific criteria
New Mexico
All toxic Not to exceed All classes
materials 10% of 48-hr TLM of water
Utah
USPHS•Standards All uses
Wyoming
No specific criteria
The Environmental Protection Agency (5), through its Division of Water
Quality Standards, claims that:
"Mercury, silver, arsenic, cadmium, chromium, copper, lead
nickel, and zinc are heavy metal compounds present in our
waters and toxic to man in varying degrees. They are serious
pollutants because these stable compounds have persistent
and toxic effects for many years following deposit. The
heavy metal compounds chromium, cadmium, mercury, and lead
have no known biological function in animal life and can
act synergistically with other substances to increase tox-
icity. Marine organisms, especially shellfish, readily take
up and concentrate these heavy metals, which are thereafter
ingested by man. Once in the human, their toxic effects are
cumulative and are harmful to the degree that the dosage and
resultant concentrations approach a lethal threshold. The
fishery industry has sustained economic losses in recent
years when unacceptable levels of mercury or other heavy
metals were discovered in fish from contaminated waters,
provoking government condemnation of the affected catches.
Fishing waters have been closed to fishermen, cutting them
off from their livelihood."
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Lead
There has been a somewhat less than reasonable reaction to problems of
lead in the environment. Unfortunately, too many biologists have been
undiscriminating with respect to the possible adverse effects of lead in
water, soil, substrate, and air. There is no evidence that lead consti-
tutes a health problem to fish in the United States. Few analytical data
have been reported on concentrations of lead in fish in natural or exper-
imental conditions. What data are available suggest that soluble lead is
not present in natural waters of the United States in concentrations
likely to be toxic to fish. There is no published evidence of any trend
toward increased concentrations of soluble lead in natural waters. Much
of the man-dispersed lead that is eventually washed into natural waters
is probably precipitated owing to the presence of carbonates, hydroxides,
and organic ligands in the water and settles to the bottom. There is no
evidence that lead precipitated on the bottom of natural waterways is
harmful to fish (1).
Finally, the basic phenomena of antagonism and synergism in biologically
active chemicals must be recognized as applying to these regional waters.
A series of analyses of1 waters from the Colorado River and tributaries
during 1970-71 gave values for lead which were always less than 0.01 ppm.
It has been suggested that "from the data available, it seems likely that
the global mean lead content for lakes and rivers lies between 1 and 10
ppb" (14).
In natural waters generally, the pH value is somewhere between 6.5 and
8.0. In the waters we have studied in the Rocky Mountain region, the
values hover around neutrality, pH 6.8 - 7.2.
Secondly, the concentration of elements is usually low, 10~%. Finally,
pure solutions of single elements are not found in nature. Wherever
dissolved C(>2 is found, as in Rocky Mountain region waters, carbonates
of lead precipitate. Hence, many of the laboratory exercises (where C02
is carefully excluded) dealing with the behavior of lead in solution are
not pertinent to the conditions in natural waters.
A short reference to technical methods is in order. Atomic absorption
spectrophotometry is the method of choice for lead in water because of
its relative simplicity. The colorimetric method is more sensitive—but
also more tedious. In our experience, the AA method is accurate within
its limitations if one acknowledges the fact of interfering substances,
notably calcium. False high lead values are found in samples that con-
tain any appreciable amounts of calcium. The use of the hydrogen lamp
blank to correct for calcium is routine in our laboratory. Random and
unaccounted "spiking" of unknowns and standards is a part of our standard
operating procedure. If these precautions are recognized, acceptable and
useful data on lead in water may be obtained.
Lead profile studies in the substrate of high lakes (10,000 feet or high-
er) in the Rocky Mountains are underway. One example from Nymph Lake may
be illustrative. A core 6.5 feet deep was taken. Lead content at dif-
ferent depths is given in the following table:
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Depth
5 - 6.5
3.5 - 5
2 - 3.5
1-2
0 - 1
Average Lead yg/gm
8
10
14
21
25
Range yg/gm
4-12 (8)
6-18 (12)
8-20 (12)
9-28 (19)
14-34 (20)
Several points are of Interest. Lead concentration has increased from an
average of 8 yg/gm in the older or deeper layers to an average of 25 yg/gm
in the younger or more superficial layers—a threefold increase during the
time span. Moreover, the range of values is greater (20 yg/gm) in the
younger layers than in the oldest (8 yg/gm); the difference in range is
2.5-fold. One may speculate on the reason for these values.
Aluminum
A number of fossil fuels may have associated with them aluminum salts.
For example, oil shale contains significant amounts of dawsonite, sodium
aluminum dihydroxy carbonate, Na Al (OH)2 C03 (16). Toxic effects of
aqueous aluminum complexes in neutral and basic media to rainbow trout
fingerlings were investigated under constantly flowing, controlled con-
ditions of concentration, pH, and temperature. Toxicities of various
concentrations were highly pH-dependent. Dissolved concentrations over
1.5 ppm aluminum caused drastic physiological and behavioral aberrations
as well as acute mortality. Toxic effects of suspended aluminum, while
they are more noticeable, at lower concentrations, are not as concentra-
tion-dependent as those of dissolved forms. The safe concentration of
either dissolved or suspended aluminum is well below 0.5 ppm. Mortali-
ties among test animals ceased almost immediately after aluminum
exposures were concluded. Recovery times for fish exposed to the various
tests were proportional to the severity of the test conditions and to the
length of exposure. Normal growth resumed almost immediately in fish
from the less severe tests, and after a period of a few weeks in fish
from the more severe tests. After up to four months recovery, the aver-
age weight of fish surviving both chronically and acutely toxic aluminum
concentrations is markedly below control average (8).
In Colorado, Utah, and Wyoming, extensive deposits of oil shale are found.
Dawsonite is present in the spent shale which must be dumped in a very
finely divided form. Aluminum salts leaching from such a dump into use-
ful trout streams would be cause for concern. It is doubtful that human
health would be in any manner threatened by aluminum salts in solution.
Mercury
The information available on mercury is inadequate to get a clear picture
of the geochemical cycle of mercury or even to make accurate estimates of
its abundance in common rock types. Data on mercury in coal and petro-
leum are scanty. Available data on mercury in natural waters indicate
that most waters contain a tenth of a part per billion to a few parts per
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billion. No data are available to permit an assessment of contamination.
Unpolluted air contains about 1 to 10 ng Hg/m . Natural pollution
caused by volatility of mercury from ore deposits of mercury or base
metals gave values up to 62 ng/m3. Industrial pollution results from the
burning of coal and perhaps petroleum and from metal smelters. No data
are available on amount of mercury discharged or on its time of residence
in the atmosphere (7).
Most samples of water from the Rocky Mountain region that we have
analyzed for mercury have less than 10 ppb. Values above that suggest a
pollution source which may be a municipal sewage outfall or a natural
source in the form of a mercury ore.
Mercury in the substratum is usually higher than in the waters. Algae
growing in streams with no detectable mercury have measurable levels
probably as a result of a natural process of concentration.
One sewage outfall in western Colorado gave 0.07 ppm mercury.
It is claimed that dilute thermal springs contain readily detectable
mercury. Sediments associated with some of these springs are rich in
mercury containing about 50 to 5,000 times the mercury content of
ordinary rocks, and the mercury contained is presumed to have been trans-
ported by the spring water. Petroleum and especially the tary residues
of petroleum contain the highest determined mercury contents. Data in
the literature for hot springs and volcanic gasses are incomplete (17).
Our analyses of waters (but not substrates) from sulfur springs in
western Colorado reveal no dissolved mercury.
The question has arisen a number of times whether there is a difference
in the amount of mercury found in eutrophic lakes as compared with the
so-called oligotrophic lakes. Mercury analyses demonstrated that 59
rainbow trout taken from an oligotrophic lake contained an average total
mercury concentration of 0.17 ppm with a standard deviation of ±0.1 ppm
and a 99% confidence interval of 0.14 to 0.20 ppm. On the other hand,
100 rainbow trout taken from a eutrophic lake had an average total mer-
cury concentration of 0.07 ppm with a standard deviation of ±0.05 ppm and
a 99% confidence interval of 0.06 to 0.08 ppm. The total mercury content
of the soil in the vicinity of the two lakes is similar. However, the
sediments of the eutrophic lake contained significantly higher levels of
mercury than the sediments of the oligotrophic lake. Water samples taken
from both lakes at various depths showed mercury levels of less than 0.1
ppb, the limit of sensitivity of the analytical method that was used.
The removal of mercury by adsorption onto organic particulate matter
probably is a key factor in the different mercury levels of fish in the
two lakes. It is this adsorption mechanism that makes the mercury from
pollution thus available for accumulation by fish that feed in the water
column. Therefore, the persistence of mercury compounds in these two
isolated lakes appears to be related to the organic character of each
lake. Accordingly, mercury pollution appears to pose a greater environ-
mental hazard in oligotrophic than in eutrophic lakes (3).
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This fact might very well explain some of the anomalous results which
have been reported from certain lakes in the United States with respect
to the amount of mercury found in fish in these lakes in which the water
showed no unusual quantities of mercury.
The fate of dissolved mercury is not always clear. Mercuric ion has been
shown to be rapidly absorbed from water by goldfish. The extent of ab-
sorption is dependent on mercury concentration and time of exposure.
This type of relationship is not unusual for almost any kind of soluble
toxicant. As has been previously shown with other metals, mercury is
known to concentrate initially in the external mucus secreted by the
fish. The presence of mercury in water appeared to stimulate the secre-
tion of mucus. It may b.e that increased volumes of mucus produced by the
fish function as a protective mechanism for the fish against rapid harm
resulting from dissolved mercury (15).
The concern which has been expressed in some quarters over the mobiliza-
tion of mercury from sediments into aquatic vertebrates may require some
modification. A recent study has been made of the aerobic mobilization
of mercury from aquatic sediments into fish. It was demonstrated that
mercuric sulfide in sediment is very slowly mobilized and picked up by
fish (9).
The relation between methyl mercury concentrations in the liver and
muscle of fish indicates the relation between accumulation and excretion
rates of methyl mercury. The total mercury content of bottom dwelling
aquatic animals is of little interest when one calculates the rate of
mercury transport from bottom dwelling animals to the fish that feed on
them. This situation obtains because the percentage of methyl mercury
in the total mercury content of the bottom is generally low, specifically
much lower than the percentage in fish, and the total mercury content is
quite variable. The methyl mercury transportation from bottom dwelling
organisms to bottom feeding fish is clearly small. By comparing the
total mercury content of 3 ecological subgroups of benthic or bottom
dwelling animals, it seems possible to separate situations where release
of mercury prevails from situations where it has ceased (11).
Mercury estimations have been made in fish from various parts of the
United States. For example, estimations were made on fish filet samples
from throughout Wisconsin and from the boundary waters of Wisconsin in
Lake Michigan, Green Bay, Lake Superior, and the Mississippi River. All
fish from Wisconsin that were analyzed contained some mercury; range of
values was from 0.01 to 0.60 ppm; the average was 0.19 ppm. The highest
mercury levels averaged 0.80 ppm; range of these highest values was from
0.06 to 4.62 ppm; these high values occurred in fish taken from below
paper mills and from below a mercury cell chlor-alkali plant. Different
species of fish vary in mercury content; the larger fish within a spe-
cies often contain higher concentrations of mercury than do smaller fish
of the same species taken from the same water. Walleye, sucker, red-
horse, crappie, and bullhead frequently show the higher concentrations of
mercury; pan fishes show lower concentrations. It is obvious that the
levels of mercury in all important fish species must be estimated before
the potential pollution problem can be evaluated adequately (12).
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Water analyses by themselves are not adequate signals of elevated mercury
levels. Biological concentrators must be included in a thorough study of
any given aquatic ecosystem.
An example of concentration of mercury by aquatic organisms is provided
by a series of studies we made on rainbow trout. The water showed no
detectable mercury. Large fish of the 12" class had values of mercury in
the muscle of about 0.02 ppm. Most fish under 8" had no detectable mer-
cury in the muscles; a few had values of 0.003 ppm or less.
Mechanism of Action
The mechanism of action by which various trace metals exert their
deleterious effects on aquatic organisms is not clear. A few in vitro
studies have thrown some light on how certain metals may exert their
toxic action (2). Relative changes in the activity of glutamic oxa-
lacetic transaminase and lactic dehydrogenase in the blood plasma from
white suckers were estimated after incubation with 49 compounds. These
agents were principally inorganic chlorides at concentrations of the
ions up to 2 mg/ml in the reaction mixture. A sequence of inhibitory
effects was arranged for each enzyme. Dose-response curves were quali-
tatively similar for most of the chemicals. The glutamic oxalacetic
transaminase was most sensitive to silver and mercury; the lactic dehy-
drogenase to palladium and mercury. Both enzymes were highly inhibited
by metals which are highly toxic to aquatic animals. Correlations were
studied between the inhibitory effect and certain physiochemical proper-
ties of chemicals; the best correltation was found between the inhibition
of the glutamic oxalacetic transaminase and the equilibrium Constance of
metal sulfides.
The effect of some trace metals in the aquatic environment may be very
subtle. A new possibly primary effect of heavy metals on fishes has been
demonstrated. Heavy metals have been observed to affect fishes so as to
cause a drop in the salt concentration in the blood serum. This change
in the ionic content of the blood can cause the fish to become weakened
and pronounced change can be fatal. Salt changes of zinc and copper in
the blood have been monitored by osmometry and show the adverse hemato-
logical effects (13).
Dissolved Oxygen
Various studies have been aimed at artificial respiration of inadequately
aerated streams and lakes. At Colorado State University, a successful
pilot study was carried out using Parvin Lake as the experimental body of
water which was aerated in order to increase the total dissolved oxygen.
Studies have been made of recent activities in river and stream aeration
by artificial techniques; it seems that a workable engineering methodol-
ogy is being developed for future river and stream aeration projects.
The engineering developments we now see being implemented are based on a
thorough review of the oxygen dynamics in rivers and streams and the
capabilities from the engineering point of view of aeration systems.
When one approaches the problem from a theoretical point of view, it
becomes evident that aeration can be used only as a "polishing" action.
It is naive to suggest that reaeration of a stream or river will solve
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all the problems of chemical overdose. Such an expectation is neither
sound nor attainable. Careful studies, based on theoretical considera-
tions compared with actual measurements made in streams and rivers,
indicate that artificial respiration or aeration can be applied success-
fully to raise dissolved oxygen levels to 5 ppm by the use of mechanical
surface aerators, diffusers, downflow contactors, and site stream mixing
(10).
This kind of treatment may find extensive use in the Rocky Mountain
region for impoundments and some natural lakes. In our experience, the
Rocky Mountain streams and rivers are well supplied with oxygen. Even
when temperatures are fairly warm in these running waters, it is rare to
find dissolved oxygen levels below 7 or 8 ppm. As a general rule, it is
fair to say that dissolved oxygen is not a limiting factor in Rocky
Mountain running waters.
Dissolved Oxygen Requirements
It is difficult to arrive at a scientifically sound and practically
feasible conclusion with respect to the minimum dissolved oxygen con-
centration in which fish can thrive. It is obvious from a study of the
literature that endurance limits have been established in the laboratory;
generally these values are probably either lower or higher than the so-
called true threshold values of tolerance in nature. A number of thresh-
old values for dissolved oxygen have been reported in the literature.
They vary widely. A major source of variation stems from different
experimental methods used. An examination of available data indicates
clearly that many of these methods are not reliable.
Interspecific differences and differences among individual fishes within
a given species are rather great with respect to sensitivity to dissolved
oxygen levels. A recent report maintains (4) that "reports of fully
developed freshwater fish being killed within a day or two by reduction
of 02 concentration to levels above 3.0 mg/1 in water of otherwise favor-
able quality are unusual and should all be regarded with some suspicion.
They cannot now be accepted as convincing evidence that reduced concen^
trations not below 3.0 mg/1 are intolerable for some fish under ordinary
conditions in nature."
In some publications, it has been suggested that high concentrations of
free dissolved carbon dioxide may aggravate oxygen deficiencies. A
comprehensive evaluation of the available literature, however, suggests
that high concentrations of free carbon dioxide probably will have virtu-
ally no effect on the response of fish to oxygen deficiency especially if
the fish are accustomed to that level of carbon dioxide concentration.
On the other hand, if the exposure to a slight increase in dissolved free
C02 is sudden in the face of reduced oxygen levels, this combination is
often lethal to fish. From the physiological point of view, it is ob-
vious that the dissolved oxygen demand of a fish increases as the amount
of dissolved free carbon dioxide in the water increases. As pointed out
previously, fish rapidly adjust themselves to high concentrations of
dissolved carbon dioxide. In nature, this fairly rapid adjustment to
elevated carbon dioxide concentration in water will occur sooner than the
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reduction of oxygen to critical levels. The available evidence indicates
that the effects of free carbon dioxide dissolved in water are not
related to the changes in pH value of that water which result from the
dissolved C02.
There are intraspecific differences in tolerance levels for dissolved
oxygen in water. These differences seem to be related to geographical
location. However, the mechanism of tolerance development and the per-
manence of any such developed tolerance is obscure at this time.
Some investigators have reported that super saturation of water with
oxygen is lethal to fish. Other investigators find that there is no
evidence for this conclusion. It is known that the excessive production
of oxygen by aquatic plants during photosynthesis can at times cause
fatal gas bubble disease in fish.
Fecundity of fish is reduced or even completely inhibited by oxygen
embryos deficiencies. The development of fish embryos can be retarded.
The size of the fish at time of hatching can be reduced and hatching can
be delayed in the presence of reduced oxygen in water.
When all the literature available on oxygen requirements of fish has been
reviewed, it is evident that the embryonic and developmental stages are
more susceptible to oxygen deficiency than are the adult stages. More-
over, it is evident that the intraspecific variations are enormous—a
fact which makes it virtually impossible to establish any one critical
threshold level for dissolved oxygen. A quotation by Doudoroff and Shum-
way (4) is pertinent: "The widely accepted conclusion of Ellis (1937)
that good, mixed fish faunas do not occur in waters in which 02 falls
below 4 or 5 mg/1 is based on unreliable evidence and is contradicted by
more reliable observations. Large numbers of fish species, including
game fishes, have been collected in polluted waters where much lower
concentrations were occurring regularly and even where concentrations
not exceeding 4 mg/1 apparently had persisted for a long time. Although
some species may be eliminated, most warm water species evidently will
continue to inhabit such (^-deficient waters if the water quality is not
otherwise too unfavorable."
It might be contended that the available fish food organisms necessary
to support a healthy fish population might be oxygen dependent. It seems
more likely, however, that the species of fish food organisms more tol-
erant of oxygen deficiency will increase in abundance in waters which are
heavily enriched by organic material. The more sensitive species will
disappear leaving less competition for the hardier species. Consequently,
if the oxygen deficiency is not great enough to retard the growth of fish,
one cannot conclude that the deficiency will impair the fish food resour-
ces. It seems probable that if the ambient water is not directly poison-
ous to fish and fish food organisms, the oxygen concentration itself will
not be limiting for an abundant fish food organism population.
As a general evaluation, Doudoroff and Shumway (4) hold that:
There is evidently no concentration level or percentage of
saturation to which 02 content of natural fresh waters can
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be reduced.without causing or risking some adverse effects on
the reproduction or growth and production of fishes inhabiting
these waters. Yet, large reductions are not incompatible with
the continued existence of some valuable fisheries.
Water quality criteria on which regulatory standards designed
for protection of fisheries in waters receiving wastes are to
be based cannot be properly formulated without reference to
the pertinent natural characteristics or the conditions of
the waters and to desired levels of protections of fisheries.
These levels of protection must be determined on the basis of
socio-economic considerations. Attention to differences of
waters and natural properties, such as 0£, that vary over a
wide range, is essential because of associated differences of
fish faunas inhabiting the waters and differences in natural
productivity of the waters.
The use of kill-no-kill data to establish acceptable concentrations of
oxygen for fishes is unwarranted. It is Important to use some Index or
series of indexes more sensitive than mere death of the adult fish. Such
criteria as incipient lethal or minimal oxygen concentrations tolerated
indefinitely by 50 percent of the fish tested are critera of questionable
value which in the past have been estimated with uncertain reliability.
References Cited
1. Aronson, A. L. 1971. Biologic effects of lead in fish. J. Washing-
ton Acad. Sci. 61 (2):124-128.
2. Christensen, G. M. 1971. Effects of metal cations and other chemi-
cals upon the in vitro activity of two enzymes in the blood plasma
of the white sucker. Chem.-Biol. Interactions for 1971/72:351-361.
3. D'ltri, F. M., C. S. Annett and A. W. Fast. 1971. Comparison of
mercury levels in an oligotrophic and an eutrophic lake. Marine
Tech. Soc. J. 5(6):10-14.
4. Doudoroff, P. and D. L. Shumway. 1970. Dissolved Oxygen Require-
ments of Fresh Water Fish. Food and Agr. Organization, Fisheries
Tech. Paper #86. FIRI/T86, Water Pollution. Food and Agr. Organi-
zation of the U.N., Rome.
5. Environmental Protection Agency. 1971. Mercury and Heavy Metals.
Office of Water Programs, Washington, D.C.
6. Fisheries Research Institute. 1971. Response of Teleost Fish to
Environmental Stress. Washington University, Seattle. Water Pollu-
tion Control Research Series, Government Printing Office Reference
#EP2.10:18050EBK02/71.
7. Fleicher, M. 1970. Mercury in the Environment. Geological Survey,
Professional Paper #713.
8. Freeman, R. A. and W. H. Everhart. 1971. Toxiclty of aluminum
hydroxide complexes in neutral and basic media to rainbow trout.
Transactions of the American Fishery Society 100(4):644-658.
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9. Gillespie, D. C. and D. P. Scott. 1971. Mobilization of mercuric
sulfide from sediment into fish under aerobic conditions. J. Fish-
ery Research Board of Canada 28:1807-1808.
10. JBF Scientific Corporation. 1971. Engineering Methodology for
River and Stream Reaeration. Burlington, Mass. Available from
National Technical Information Service, //PB-208-818.
11. Jerneloev, A. and H. Lann. 1971. Mercury accumulation in food
chains. Oikos. 22:403-406.
12. Kleinert, S. J. and P. E. Degurse. 1971. Mercury Levels in Fish
from Selected Wisconsin Waters (a preliminary report). Research
Report //73. Wisconsin Dept. Natural Resources, Madison.
13. Lewis, S. D. and W. M. Lewis. 1971. The effect of zinc and copper
on the osmolality of blood serum of the channel catfish Ictalurus
punctatus Refinesque, and Golden Shiner Notemigonus crysoleucas
Mitchill. Transactions of the American Fishery Society 100(4):639-
643.
14. Livingstone, P. A. 1963. Chemical Composition of Rivers and Lakes.
Geological Survey Professional Paper #440-G. U.S. Government Print-
ing Office, Washington, D.C.
15. McKone, C. E., R. G. Young, C. A. Bache and D. J. Lisk. 1971.
Rapid uptake of mercuric ion by goldfish. Env. Sci. and Tech. 5(11):
1138-1139.
16. Welles, C. 1970. The Elusive Bonanza. Dutton, New York.
17. White, D. D., M. M. Hinkle, and I. Barns. 1970. Mercury contents
of natural thermal and mineral fluids. In Mercury in the Environ-
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2nd printing. C. C. Thomas, Springfield.
149
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150
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NITRATES: HUMAN AND ANIMAL HEALTH
J.:Osteryoung
The element nitrogen is an Important part of the biocycle and is a
substantial component in primary rocks. With the exception of nitrogen
gas, N2, all of its inorganic forms are labile with respect to oxidation
and reduction in the environment and very soluble in water. The many
physical, chemical, and biological sources and sinks of the various forms
of nitrogen make it difficult to identify the source of any nitrogen
compound and to estimate the nitrogen balance, even in a restricted area
such as a small watershed. The best known aspect of nitrate pollution
is the addition of undesirable amounts of nitrate to surface waters which
accelerates the process of eutrophication. However, sufficient exposure
of humans and other mammals to nitrate can cause methemoglobinemia and
has been implicated in a variety of other health problems. This paper
describes the sources and transport of nitrogen in the environment and
discusses possible health effects of exposure to nitrates.
The Occurrence of Nitrogen in the Environment
Nitrogen occurs in many chemical forms in the environment. Table 1 shows
the total amount of nitrogen in various natural reservoirs of this
element (1). Although the largest amount of nitrogen is contained in
the atmosphere, this source is relatively unimportant in most problems
involving the nitrogen cycle because it consists of nitrogen gas (N£),
which is extremely inert to chemical reaction. In other words, the rates
of oxidation or reduction of nitrogen gas are much slower than the rates
of many other nitrogen species interconversions.
TABLE 1
Total Nitrogen in the Environment (g/cm2)
Primary rock 32,000
Atmosphere 755
Fossil N. (sedimentary rocks) 70-110
Surficial deposits 2 x 10~5
The most important characteristics of the element nitrogen are the variety
of its chemical forms found in nature, the rate of conversion from one
form to another, and the high solubility of many of these forms in water.
Table 2 shows some compounds of nitrogen which are involved in the bio-
cycle. Living matter contains nitrogen in complex molecules such as
purines, proteins, porphyrins, and others. As indicated in Table 2, these
compounds contain nitrogen in a reduced state, and most commonly in the
most reduced state. The primary products of organic matter decay, hydro-
cyanic acid, urea, and amines and amino acids, are broken down further
into ammonia or possible hydroxylamine, depending on the valence state of
the precursor.
151
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TABLE 2
Some Forms of Nitrogen in the Environment
Name
Ammonia
Hydroxylamine
Nitrous acid
Nitrite
Nitric acid
Nitrate
Hydrocyanic acid
Urea
Amines
Formula
NH3
NH2OH
HN02
N02
HN03
NO I
HCN
(NH2)2CO
R-N-R'
1 r
Valence
-III
-I
III
V
-III
-III
/s=v ~IZI
-4_>^
Porphyrins
Proteins
Purines
Figure 1 shows a distribution diagram for the important inorganic forms
of nitrogen in the environment. The diagram is drawn for a neutral water
solution with total concentration of 10~% nitrogen. Also shown is the
reducing power of the system as a function of the oxygen partial pressure
in equilibrium with the water. The circled point corresponds to the
oxygen partial pressure in the standard atmosphere. From this figure, we
can see that under aerobic conditions the stable form of nitrogen is
nitrate, that nitrite has a very narrow region of stability, and that
systems have to be substantially anaerobic to contain ammonia (or ammon-
ium ion) as the most stable form. Considering the equations for reduction
of nitrate and nitrite to ammonia
9H
N02 + 7H
8e = NH3
6e = NH3
3H20
2H2Q
it is apparent that the reduction takes place more readily in acid solu-
tion. Therefore, in solutions with pH < 7, the .region of stability
for NHit+ extends to more oxidizing potentials than it does in neutral
solution.
In Figure 1, nitrogen gas is not included because of its chemical inert-
ness. However, the other interconversions suggested are also slow in
comparison with many common reactions in aqueous solution. In nature,
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_o
I
+10
Figure 1. Distribution of inorganic nitrogen species as a function of
oxidizing power and pH. pe = FE°/2.3RT, where F is the Faraday, R is
the gas constant, T is the temperature in °K, and E° is the reduction
potential vs. the standard hydrogen electrode.
153
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interconversions of ammonia, nitrite, and nitrate are typically mediated
or catalyzed by microorganisms, riitrosombnas freing the mediator for the
ammonia/nitrite conversion and nitrobacter for the nitrite/nitrate con-
version. It should be emphasized that the rate of the uncatalyzed
oxidation or reduction of any of these species to another is quite slow,
and that therefore biological processes dominate the rates of change of
nitrogen containing systems under most conditions.
Ground Water Nitrate Levels
Ranges and typical levels of nitrogen in water and in rocks are shown in
Table 3 (1 ). Both surface water and ground water usually have nitrate
as the predominant form, and the concentrations in ground water are
typically higher. Ground water in contact with rocks can leach nitrate
and also accumulate ammonium ion through exchange of calcium, magnesium,
or sodium ions in the water with ammonium ions in the rock (2 )• Potas-
sium and ammonium ions react similarly with clay minerals, and therefore
high potassium concentrations in water should compete with ammonium ions
for fixation in minerals, and release fixed ammonium ions through an ion
exchange mechanism. One might expect rather high concentrations of
nitrate in ground waters in contact with peat or oil shale because of
their very high nitrate content.
TABLE 3
Nitrogen Content (as nitrate, ppm)
Surface Water 0-100
Ground Water 0-1,000
Igneous Rocks ^ 200
Sedimentary Rocks ^ 2,200
Peat ^ 70,000
"Unpolluted" Water 5-10
In soils almost all of the nitrogen is "fixed," that is, locked up in
insoluble forms in clays or humic compounds; typically 0.1% or less is
present as free nitrate or ammonium ions which can be leached into water
and are available as plant food (2). For this reason, we focus our
attention on nitrate and ammonium as sources of water pollution. The
main sources of nitrates in water are natural aerosols (ammonium sulfate),
precipitation, fixation, by microorganisms, organic matter, agricultural
and industrial wastes, and rocks. The relative importance of these
sources varies with region.
Table 4 summarizes data on the nitrogen content of precipitation (1).
Although the amounts are small compared with those from sources such as
fertilization, in grasslands or other relatively undisturbed environments
they can be significant. Keeney and Gardner (3) point out that the
amount of nitrogen required to bring a soil percolate to the 45 mg/1
154
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nitrate level is 2.27 Ibs/acre-in. For example, if deep percolation out
of the root zone is 6 in/yr, only 13.6 Ib/acre/yr of nitrate would be
required. This corresponds to 3.9 tons/mi2/yr, which is in the normal
range for nitrogen in precipitation.
TABLE 4
Nitrogen in Precipitation (Expressed as Nitrate)
NH3 (mg/1) * 1-2
N02 + NOa (mg/1) 'v. 0.2-1
NH3 (tons/mi2/yr) 0.5-14
NO^ (tons/mi2/yr) 0.25-3
Total Nitrogen (tons/mi2/yr) 0.7-16
(Fertilization (tons/mi2/yr)) (100-1900)
Symbiotic nitrogen fixation through leguminous plants can be an important
source of nitrogen in soils in intensively cropped areas. Legumes have
been estimated to add in the range 50-250 ton/mi2/yr nitrate, which can
amount to a significant fraction of total soil nitrate added per year.
Nonsymbiotic fixation is more difficult to estimate. The amounts of
nitrogen fixed are much less than for symbiotic fixation, and it is not
clear that existing data are applicable to real field situations. Total
microbiological nitrogen fixation is undoubtedly an important source of
soil nitrate in heavily farmed areas with extensive use of nitrogen
fixing cover crops, but is unimportant in arid areas or areas of fallow
soils.
The most important non-agricultural sources of nitrate pollution are
domestic sewage and percolate from refuse (as from a sanitary landfill).
The former has nitrate concentrations in the range 90-180 mg/1 while the
latter is in the neighborhood of 1300 mg/1. These can be extremely
important sources of surface and ground water pollution in heavily popu-
lated areas and in arid or semi-arid areas. The typical "sanitary
landfill," which is in practice usually a dump, should be suspected as
a point source of nitrate pollution of ground water. The main nitrogen
component of raw sewage is ammonia. Biological treatment oxidizes
ammonia and organic forms of nitrogen to nitrate. The removal of nitrate
(or ammonia) from wastewaters is under investigation, but no domestic
sewage plants now have that capability (4-6).
Agricultural nitrate pollution is presently a much discussed and little
understood subject ( 7). Commoner and others have taken the position
that the nitrate burden in surface and groundwaters is due primarily to
the heavy application of inorganic nitrates common in modern farming (8).
Some criticisms of this point of view simply state that it isn't neces-
sarily so, and if it is so, it is unimportant in light of the task of
growing food for the world's starving millions (9). Other more substan-
tive reviews of this question have provided insight to the nitrogen
balance problem under specific conditions but have concluded that it is
unwise to generalize.
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In studies of bromegrass in North Dakota, Power found 17% of applied
nitrogen lost under dryland conditions and 23% lost under irrigated con-
ditions (10). However, under the dryland conditions, nearly half of the
applied nitrogen appeared as soluble nitrogen in the soil. With the
same fertilizer application (180 Ib/acre first year, 270 Ib/acre second
year), the irrigated bromegrass contained 70% of the applied nitrogen
while the dryland bromegrass contained only 36%. The implication is that
the dryland was overfertilized. Stewart'_et'al. (11) studied the middle
South Platte area of Colorado and found soil nitrate levels shown in
Table 5. Deeply rooted high protein crops such as alfalfa deplete soil
nitrate so that the level is even less than in native grassland. Also,
the nitrate levels in dryland culture are much higher (probably due to
low organic matter content) than previously thought, and therefore,
nitrate leaching from these soils is undoubtedly significant. Finally,
this work concluded that despite the much higher levels of nitrate near
feedlots, the total area of irrigated farmland was sufficiently great
that feedlot contribution to nitrate pollution of groundwater was less
than that of irrigated farmland. This is in contrast to the opposite
assumption made in the northern Missouri area (12).
TABLE 5
Average Total Nitrate, 0-20 ft, Ib/acre
Alfalfa 79
Native grassland 90
Cultivated dryland 261
Irrigated, not alfalfa 506
Corrals 1436
Stout and Burau (13), after extensive investigation of nitrate profiles
in the Arroyo Grande basin, a heavily cropped area near San Luis Obispo,
California, conclude that the primary source of nitrates to ground waters
is tillage of native soils. The most important practical conclusion to
be drawn from their work is that in areas such as San Luis Obispo with
large populations and intensive farming, ground water levels of nitrate
will prohibit the use of shallow aquifers for domestic water supply and
either a surface water source or a primordal deeper aquifer must be
used. Martin et al. concluded that farming practices in general rather
than fertilizer application itself are most important in determining the
extent of nitrate pollution (14). Prevention of erosion, minimum tillage
(which reduces the extent of oxidation of organic matter to nitrate), and
use of deep rooting cover crops such as alfalfa are suggested as farming
practices which reduce the extent of nitrate loss. Smith takes a some-
what similar, if less constructive view, but he emphasizes the importance
of domestic and animal wastes in rural groundwater (wellwater) pollution
(12). Goldberg has summarized, but not evaluated, data on contributions
of nitrate from various sources to water supplies (15).
156
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The reason for controversy over the sources of nitrate pollution is that
the reservoirs of nitrogen are large compared with small amounts of
mobile nitrate; small differences in soil type, agricultural practices,
etc. which slightly change rates of conversion from reservoir or fixed
nitrogen to mobile nitrogen (mainly nitrate) make it nearly impossible
to generalize the results of any observation or experiment. Commoner has
attempted to solve this identity problem by recognizing that different
sources of nitrogen may have slightly different isotopic nitrogen abun-
dances, and therefore, the ultimate source of nitrate in water may be
determined by its isotopic composition. This method was applied to the
Sangamon River basin in central Illinois, and it was concluded from data
obtained that fertilizer was the source of 50-60% of the nitrate in
surface waters of the area (16). This approach has been criticized by
Hauck et a.1. (17), and although the reply seems adequate (18), it is
difficult for one not personally experienced in this area to judge.
Lower
la
Rive
Figure 2. The Lower Cache La Poudre River Basin.
157
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Assessing the importance of fertilizer runoff has specific implications
for the environmental health specialist as well as the soil scientist and
agriculturist. The Colorado River is an example of a multiple use surface
water which is heavily polluted with nitrate and salts in general from its
headwaters down, and is also used by large cities as domestic water supply.
Agricultural practices in Colorado and other western states inevitably
affect the quality of domestic water supplies in cities such as San Diego
and Los Angeles. On a smaller scale, the severe pollution of family
water supply wells, especially in Missouri, Minnesota, and Colorado has
generally been attributed to local spot sources, usually feedlots or
improper human waste disposal (14). Most studies have shown that lateral
movement of nitrates from these sources is 300 feet or less, so that the
source is isolated in the absence of high water table. Howeverj it should
be pointed out that there are numerous instances of new wells tapping high
nitrate water in areas where there has been little prior human activity.
We have tried to determine the source of nitrates in areas in Colorado
which have a long history of high nitrate levels in public water supplies
(19). Figure 2 shows a portion of the lower Cache La Poudre River Basin
near Fort Collins, Colorado. Fort Collins and Greeley obtain their
municipal water from the foothills of the Rocky Mountains; this water is
unusually pure. The other towns shown obtain water from local wells.
Of these, Nunn, Pierce, and Eaton have rather high nitrate levels (30-
160 mg/1) and Ault and Windsor very low levels. The town of Nunn, shown
in Figure 3, is especially interesting because although nitrate levels
there are consistently over 70 mg/1, there is no apparent source of
nitrate pollution. Nunn has a population of 228, and it is isolated in
the middle of a dryland wheat growing area where no fertilizer is used.
The two city wells (1 and 2 in Figure 3) are drilled and properly sealed
but shallow (39 and 52 feet, respectively) with water levels of 12 and
30 feet. Groundwater flow is NNW to SSE, and there is little human
activity in the area NNW of the town. Fluorescein dye tests do not show
direct contamination of drinking water wells by septic tanks in the area.
All groundwater samples taken at si'tes shown in Figure 3 gave nitrate
levels above 45 mg/1 except No. 8, which is east of the Nunn groundwater
flow pattern, and other sites, not shown in Figure 3, where a lower lying
aquifer (^ 200 feet) was sampled. This is an apparent case of "natural
pollution" which has exposed the Nunn population to nitrate levels in
public water as high as 160 mg/1 for at least a decade.
Nitrate Content of Foods
The main sources of nitrate exposure for humans are water and foods.
Foods fall into two categories, those with no deliberately added nitrates
and those with nitrates (or nitrites) added during processing.
Lee (20) has recently reviewed some aspects of nitrate effects on human
health and presents collections of data for nitrate and nitrite content
of fresh and processed foods. Spinach, beets, rhubarb, lettuce, and
cabbage have been found to have nitrate concentrations in the 0.1 - 0.5%
range. Results of different investigators vary widely. This may be due
in part to faulty analysis, but it can easily be accounted for by differ-
ences in fertilizer application, rainfall, etc. The natural accumulation
158
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Figure 3. The town of Nunn, Colorado, showing groundwater sampling sites
and drainage patterns to the north and west. No. 1 and 2, City of Nunn
domestic water supply wells; E%^ , city dump.
159
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of nitrates in produce, particularly leafy vegetables, is highly dependent
on agricultural practices and natural conditions. Fresh produce contains
nitrate, but little or no nitrite. During storage, especially after
processing, nitrate can be converted to nitrite. Storage above 15 C and
anaerobic storage strongly favor production of nitrite. An extensive
compilation of data on nitrate content of foods is contained in a recent
NIEHS review article (21). Methods for nitrate determination are gener-
ally considered unsatisfactory, particularly in natural products and
foods. Several recent analytical papers illustrate typical problems in
analysis for nitrate or nitrite in cheese (22), milk and milk products
(23), spinach (24), meat products (25), and baby foods (26,27).
Many processed foods contain nitrate or nitrite used as a preservative or
for color enhancement. Section 121.1064 of Title 21 of the Code of Fed-
eral Regulations contains the following provisions regulating the use of
sodium nitrite in foods:
1. As a preservative and color fixative in smoked, cured tuna
fish products not exceeding 10 ppm in the finished product.
2. As a preservative and color fixative, with or without sodium
nitrate, in smoked, cured sablefish, cured salmon, and smoked,
cured shad riot exceeding 200 ppm and the level of sodium
nitrate not exceeding 500 ppm in the finished product.
3. As in (2), in meat-curing preparations for home curing of
meat and meat products with directions for use meeting the
specifications of (2).
Section 121.1230 specifies conditions for using sodium nitrite in combi-
nation with sodium chloride in the preparation of smoked chub (whitefish)
to aid in inhibiting outgrowth and toxin formation from Clostridium
botulinum type E. The sodium nitrite content of the edible portion of
the finished product must be not less than 100 ppm and not greater than
200 ppm.
Under title 9, Section 318.7, sodium and potassium nitrite and sodium and
potassium nitrate are authorized for use in cured meat products under
conditions providing no more than 200 ppm nitrite (sodium nitrite) in
the finished product.
In addition, baby foods are allowed to have no more than 25 ppm nitrite.
Analyses carried out by the Consumer and Marketing Service, USDA, of a
variety of baby foods containing eggs or meat showed nitrite as sodium
nitrite in the range 0-28 ppm and nitrate as sodium nitrate in the range
0-175 ppm (28). It is interesting that with the exception of Gerber
products, the manufacturer is not identified. In general, each sample
had "none" or >_ 13 ppm sodium nitrite and "none" or >^ 20 ppm sodium
nitrate. However, Lee (20) presents a summary of results for nitrate
content of baby food vegetables by different workers, 1949-1969, which
shows nitrate in the 1000 ppm range for many samples and substantial
concentrations (say, >30 ppm) in most samples. The Joint FAO/WHO Expert
Committee of Food Additives in 1962 recommended no acceptable dose level
of nitrates and nitrites for infants below six months of age (29). A
summary of the most recent report of this committee re-emphasized the
160
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importance of reducing the nitrate and nitrite intake of infants to a
minimum (30).
The origin of standards for nitrates and nitrites in meats is obscure.
Apparently the standard of less than 200 ppm sodium nitrite in the fin-
ished product resulted from experiments made by a meat processing company
under USDA supervision in which it was found that cures with the desired
properties (taste, color, etc.) could be obtained with nitrite treatment
under conditions resulting in meeting this standard (31). That is, the
standard was written to fit a rather limited set of experiments suited to
the needs of the meat processing industry. Investigation in Britain in
1940 demonstrated that bacon, one of the worst offenders (as high as 0.27%
nitrite after storage), can be prepared at the 10 ppm nitrite level with
rio impairment in the curing process (32). Although one must be realistic
about quality control problems, present knowledge of the health effects of
nitrates and nitrites would suggest the adoption of lower tolerances; for
these substances in foods. This is the general tone of a recent govern-
ment report on nitrates and nitrites in foods (33). Reporting of the
controversy surrounding the food additives problem has been evenhanded,
even thoughtful, in scientific trade journals (34) but less accurate and
more frivolous in corresponding medical journals (35).
Nitrate Toxicology
Those adverse health effects involving nitrate for which a mechanism is
known or reasonably suspected involve, as a first step, the reduction of
nitrate to nitrite. We shall first outline the known or suspected effects
of nitrate and related compounds on human and animal health, and then
discuss in more detail three problems deserving special attention, methe-
moglobinemia, chronic cardiovascular toxicity, and nitrosamine toxicity.
Organic and inorganic nitrates and nitrites have two primary pharmacolog-
ical actions: the relaxation of smooth muscle, especially small blood
vessels, and reaction with hemoglobin to form methemoglobin (36). Each
compound differs from the rest in the relative efficiency of these two
actions. For example, amyl nitrate is an effective vasodilator used for
symptomatic relief from angina, while sodium nitrite (or nitrite ion) is
especially effective in the formation of methemoglobin. Acute toxic reac-
tions to nitrates are based on these two properties. Organic nitrates
with high lipid solubility are readily absorbed through the skin or mucosa
or, if the vapor pressure is sufficiently high, through the lungs. Water
soluble inorganic nitrates or nitrites must be ingested (or injected) to
produce toxicological effects. The metabolism of nitrates is not known,
but inorganic nitrates or nitrites are rapidly absorbed in the upper in-
testine and excreted in substantial amounts.
Intoxications which primarily produce methemoglobinemia are characterized
by acute cyanosis, nausea, vomiting, collapse, and so on. Cyanosis is
clinically evident when the methemoglobin level reaches 10-15% of the
total pigment circulating in the blood; levels of 60% produce stupor while
the lethal range is probably 70-85%. There is a reasonably good correla-
tion between the severity of the intoxication and the methemoglobin level.
However, some cases of cyanosis have been reported with methemoglobin
levels as low as 3% (37). Infants are especially at risk, because of
low gastric acidity which promotes nitrite formation in vivo from
161
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ingested nitrate, and because of the susceptibility of fetal hemoglobin
to methemoglobin formation.
The standard treatment for methemoglobinemia consists of methylene blue
injections; the mode of action is not understood, but the treatment is
universally successful. Although ascorbic acid is effective in reducing
methemoglobin concentrations, its use is not appropriate in the case of
acute intoxication. The use of nitrite as treatment in cases of acute
cyanide poisoning has been substantially discredited.
Intoxications which primarily cause smooth muscle relaxation produce
cardiovascular and central nervous system reactions. Initial shock is
produced by dilation of postarteriolar vessels; this vasodilation is
not blocked by any recognized drug, and in fact arteriolar constrictors
probably should be prohibited in treatment of the condition. Increased
intracranial pressure and cerebral anoxia are implicated in nervous
symptoms. Circulatory inadequacy is complicated by methemoglobinemia,
resulting in cyanosis and anoxia. With exception of treatment for sec-
ondary methemoglobinemia, supportive symptomatic treatment, including
transfusion, is all that is available.
There are numerous reports in the literature of acute nitrate poisoning,
often resulting in death, due to deliberate or accidental ingestion of
drugs such as amyl nitrite or nitroglycerine, ingestion or superficial
contact with various dyes and polishes containing organic nitro compounds,
consumption of water high in nitrate (in infants), and ingestion of proc-
essed foods not meeting U.S. government regulations. One particularly
striking case involves acute nitrite poisoning with severe cyanosis in
a healthy adult patient normal in methemoglobin reductase activity; the
poisoning occurred from eating sausage well within the standards (180 ppm
sodium nitrite) (38). Because conditions in the rumen are especially
conducive to production of nitrite from nitrate, cattle, sheep, etc. are
especially susceptible to nitrate poisoning (39).
Nitrates apparently also interact with vitamins or vitamin metabolism.
High nitrite exposure causes Vitamin A deficiency; evidence suggests on
the one hand that this is due to impaired thyroid function which inhibits
carotene transformation to Vitamin A (40) and on the other that it is
due to direct destruction of carotene and Vitamin A in the intestinal
tract (41). Significantly higher levels of methemoglobin are produced
by nitrite in animals exhibiting Vitamin C deficiency than in those with
normal Vitamin C levels (42). Vitamin C is capable of reducing methemo-
globin and is used in management of hereditary methemoglobinemia (36).
Epstein has reported on the involvement of sodium nitrate in a case of
palindromic rheumatism (43).
Methemoglobinemia. The relations of nitrite and nitrate consumption to
clinical methemoglobinemia have been comprehensively reviewed by Lee (20).
The etiology, diagnosis, and treatment of this condition as described
above is well established. Although some populations with impaired
methemoglobin reductase activity, pregnant women, and people stressed
by starvation are at greater risk from nitrate exposure than the general
162
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population, the highest risk group is infants under 9 months. In most
cases, the major exposure to nitrate in this age range is from water;
this exposure can easily be controlled. Therefore, public health
officials have a special responsibility to prevent this condition by
finding if nitrate levels in local water supplies are dangerously high
and publicizing this problem if it exists.
Infant methemoglobinemia is relatively well-known in the midwestern Unit-
ed States and most of the reported cases are from this area. However,
failure to report or incorrect diagnosis of mild methemoglobinemia may
result in substantial underestimate of the prevalence of the condition.
Methemoglobinemia in infants is often associated with gastroenteric in-
fection, probably because impaired adsorption of nitrate in the intestine
increases the rate of conversion' of nitrate to nitrite. Diarrhea has
been reported as an effect of nitrites (20). Change in regimen as treat-
ment for diarrheal diseases might often remove the source of nitrates and
automatically reduce blood methemoglobin levels. Adequate awareness of
this problem on the part of public health professionals should eliminate
mortality and substantially reduce morbidity due to elevated blood
methemoglobin.
The effects of subclinical methemoglobinemia or chronic elevation of
methemoglobin levels above the normal range are unknown. Kohl je_t al. are
now attempting to determine normal values for methemoglobin in blood and
to relate methemoglobin levels to nitrate consumption and biochemical
parameters of blood (44). There is reason to suspect that elevated
methemoglobin levels enhance atherogenesis in the rat (45). It is known
that chronic exposure to carbon monoxide with resulting high levels of
blood carboxyhemoglobin accelerates the development of atherosclerosis
in rabbits and squirrel monkeys (46,47). The effects of carbon monoxide
are also more severe at higher elevations. One might expect elevated
methemoglobin levels to exhibit the same characteristics. These facts
ta.ken together show the importance of discovering the relation between
nitrate consumption and methemoglobin levels and of carefully studying
the health effects of elevated levels. The physiological connection with
atherosclerosis also has a bearing on the epidemiological data of the
following section.
Hypertension and Sudden Death. Morton has investigated the relations
among drinking water constituents, hypertension, and chronic cardiovascu-
lar disease in Colorado (48). He found no correlation between chronic
cardiovascular disease mortality (ischemic heart disease, vascular lesions
of the CNS, and general arteriosclerotic and peripheral vascular disease)
and altitude or geographic area. However, both hypertensive heart dis-
ease mortality and hypertension prevalence were significantly greater at
lower altitude. In addition, hypertension mortality and prevalence were
higher in river basins with greater water hardness and with higher nitrate
concentration. Although the use of mean nitrate values in public water
supplies as an index of exposure of the sample population is not very
satisfactory, criticisms of this study all suggest that the correlation
between nitrate exposure and hypertensive disease is underestimated.
The hypotensive effect of organic nitrates is well known and has been
suggested as the cause of elevated diastolic pressure among workers in
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the explosives industry. Morton has reviewed the industrial toxicological
problem of the explosives industry (49). "Monday morning angina" includ-
ing sudden death has clearly been established as an occupational hazard
of explosives workers.
Schmidt and Knotek have examined the incidence of infant methemoglobin-
emia in Czechoslovakia and suggest nitrate poisoning may be responsible
for 10-20% of the cases of sudden death in infants up to three months of
age (50). The sudden infant death syndrome (crib death) is poorly
understood, and furthermore, epidemiological study of this syndrome is
difficult because of problems in determining cause of death and fads in
reporting. This makes it hard to obtain reliable mortality data. In
spite of pessimistic views of further possible contributions of epidemi-
ology to the understanding of this syndrome, several factors suggest that
the role of nitrate exposure should be explored (51). The wide range of
methemoglobin levels associated with onset of clinical methemoglobinemia
(3-15%) shows individual variation which might also be prevalent at lower
levels. Therefore, some infants, particularly premature and low birth
weight infants, might experience hypoxia at methemoglobin levels gener-
ally considered normal. These groups have a higher incidence of crib
death. Studies in Ontario, Canada have shown that 85% of verified cases
of crib death are of infants exclusively bottle-fed. These data led to
the hypothesis that hypersensitivity to cow's milk is a contributing
factor. However, the hyperallergenic hypothesis has not been substanti-
ated, and association of crib death with bottle-feeding might also impli-
cate the water used in formula preparation. Crib death occurs at rates
of 2-3 per 1,000 in the same age cohort that infant methemoglobinemia is
prevalent, and it accounts for about 20% of all infant mortality. We
have not found any reports which have examined the hypothesis that nitrate
exposure is a contributory factor in crib death, but we feel such a study
would be valuable.
Nitroso Compounds. The general and acute toxicity, tetratogenicity,
mutagenicity, and carcinogenicity of a variety of nitrosamine compounds
in mammals is well established (52,53,33). Experiments show that about
three-fourths of the nitrosamines tested produced lesions in test animals.
Dose-response relationships, no-effect levels, limits of toxicity, and
margins of safety are unknown. The specificity of carcinogenic activity
of various nitrosamines provides a basis for epidemiological studies in
humans. Recently, dimethyInitrosamine (DMNA) in an alcoholic beverage
called Kachasu has been implicated in the high incidence of esophageal
cancer in East Africa (54,55).
There is no question that the nitrosamines are potent carcinogens which
can be dangerous to human health. In addition, they have the remarkable
property that a single dose can induce cancer (56). However, human ex-
posure and the relation of exposure to nitrate and nitrite exposure are
not presently known. Major areas of concern are the presence of nitro-
samines in foods, especially cured meats and fish, and in vivo synthesis
of nitrosamines from nitrates and naturally occurring amines or drugs.
Nitrosamines are compounds of the form RR'N-NO where R and R? represent
some organic moiety. They can form by reaction of nitrite and various
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secondary amines, quaternary ammonium ions, urea, etc. Therefore, the
occurrence of nitrosamines in foods or the production of nitrosamines in
vivo depends on the presence of both nitrate and a suitable nitrogen-
containing substrate under chemical or microbial conditions which
facilitate the reaction. Trimethylamine oxide is present in relatively
large amounts in marine fish used to make fish meal to which nitrite is
added as a preservative. Hepatotoxicity in sheep and mink has been
caused by DMNA from this source (57-60). DMNA has also been found in
cured meat and fish products (53,61-64). Various investigators have
found that nitrosamines can be formed in vivo or under physiologic con-
ditions in vitro (65-67). Lijinsky has suggested that many common drugs
which are secondary amines may react in vivo to produce carcinogenic
nitrosamines (68). It has also been suggested that the heavy losses of
livers of feedlot cattle is due to formation of nitrosamines from nitrates
and amines present in feeds (69).
Investigation of this problem is severely hampered by the lack of adequate
analytical methodology. There are a wide variety of nitrosamines, they
are in general labile compounds which are easily formed or destroyed by
sample treatment, and there are many interferences in the usual analytical
procedure. The most exacting digestion-distillation-extraction-GLC-MS
techniques give apparently reliable identification and quantitation but
are far too expensive for routine analysis required in survey or monitor-
ing programs. All phases of investigation of the nitrosamine problem
urgently require more reliable and less expensive analytical methods.
This subject is discussed in several recent articles and reports (53,67,
70,71).
The presence of nitrosamines in the human environment has been called a
menace and a possible human health hazard (72,73). The latter view seems
the balanced one at this point. The known potent toxic effects of these
compounds and their suspected presence in humans from ingestion or syn-
thesis in vivo argues first that research on this problem should proceed
in all fields at a fast if not urgent pace, and second that human intake
of the known precursors of nitrosamines, especially nitrite, should be
held to levels as low as practical.
Exposure to Nitrate
Estimation of individual exposure to nitrate is important in any epidemi-
ological study and in the setting of standards. Van Camp has reviewed
the process by which PHS set the drinking water standard at 45 mg/1
nitrate (10 mg/1 nitrogen) and concluded that it is based primarily on
retrospective studies of incidence of infant methemoglobinemia (74).
There are two interesting papers which try to establish some theoretical
range for an appropriate standard.
Burden has reviewed data on nitrate toxicity in adults and infants and in
animals (75). He concludes that the lethal dose is about 20 mg/kg nitrite
nitrogen or 66 mg/kg nitrite. This would correspond to about 90 mg/kg
nitrate if there were complete conversion. He then assumes that the per-
missible dose is 0.2 times the lethal dose, or 4 mg/kg nitrite nitrogen.
Assuming complete conversion, he concludes that permissible limits of
165
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nitrate nitrogen in water are 6 mg/1 for infants in the tropics and 45
mg/1 for adults in the tropics, or 24 mg/1 and 240 mg/1 in England. These
figures are based upon estimates of water intake and calculated for 3 kg
infant weight and 60 kg adult weight. The corresponding figures for
nitrate concentrations are 27, 200, 106, and 1600 mg/1. Dry climates were
not considered, nor was individual variation allowed for. Still, the
lowest calculated level, 27 mg/1 nitrate, is well below the current USPHS
standard for nitrate.
Winton jit ai^. (76) have calculated the hypothetical dose of nitrate
required to convert 10% of hemoglobin to methemoglobin, assuming 80%
bacteriological conversion of nitrate to nitrite. At 3 months for a 5.4
kg infant, this dose would be 9 mg/kg/da nitrate, or assuming consumption
of one liter of water, 49 mg/1 nitrate or 11 mg/1 nitrate nitrogen. These
numbers are very near the present USPHS standard of 45 mg/1 nitrate (10
! mg/1 nitrate nitrogen).
I '
These approaches, of course, do not allow for individual variation, and
they are aimed primarily at preventing clinical infant methemoglobinemia.
Further epidemiological study of the chronic effects of nitrate exposure
must include estimates of individual nitrate exposure based upon nitrate
levels in water, daily water intake, dietary and food handling habits,
Vitamin C consumption, and so on. Infants are the group at greatest risk
for developing methemoglobinemia, and probably also for health problems
such as essential hypertension which might be associated with chronic
exposure to nitrates. They also have a regimen that can expose them to
much higher levels of nitrate than adults in the same household. Formula
might be made from powdered milk substitute (Similac, etc.) using high
nitrate water, while adults would get much of their liquid from canned
or bottled beverages. Infants' solid food might consist of commercial
baby foods which contain high nitrate and nitrite levels (ham and bacon
are favorites) and of vegetables, some of which are especially sensitive
to conversion of nitrate to nitrite during storage. Adults would normal-
ly have a smaller fraction of cured meats in their diet and fewer left-
over vegetables. Finally, the first and most popular meat fed to infants
is usually the ubiquitous hot dog. Lee's jocular comment that it is
fortunate that most infants don't eat much corned beef (20) displays
curious ignorance of this dietary vagary of the American public.
Summary and Conclusions
It is known that methemoglobinemia is a serious and often fatal result of
nitrate exposure. On the basis of present evidence it is almost certain
that some people are indirectly exposed to carcinogenic nitrosamines
through nitrate or nitrite exposure. Chronic "effects of nitrate exposure
are unknown but could well include hypertension and atherosclerotic
disease. There is some possibility of involvement of nitrate exposure
with sudden death in infants and adults.
Water and foods both contain nitrates, often at levels which could be
hazardous, especially to infants. In many cases, the source of nitrate
is "natural" and difficult to control (in fresh spinach, for example, or
a "virgin" water supply). In others, such as cured meat and fish products,
nitrate (or nitrite) is deliberately added.
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Both the hazards and the sources of nitrate exposure are complex. Realiz-
ing this complexity, we can nevertheless adopt policies which tend to
minimize nitrate exposure, encourage public health officials to be alert
to the dangers of high nitrate levels in drinking water supplies, and
move forward on the epidemiological and physiological studies required
to better assess the human and economic costs of nitrate exposure. At
this stage, certainly all steps possible in the area of education should
be taken, from requiring that methemoglobinemia be reported in disease
statistics to providing proper instruction in home economics classes on
preparation and storage of foods. It is imperative that the scientific
investigation of. this problem proceed vigorously to provide us with the
definitive information required in the difficult political process of
setting standards.
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cardiovascular toxicity of the organic aliphatic nitrates. W. E.
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C, G. Ray, Eds., University of Washington Press, Seattle, 1970.
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84:19-31, 1962. ~~~'^
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produced from sodium nitrite preserved herring. F. Ender, G. Havre,
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51:637, 1964. "~ "' ""' .'
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Cosmet. Toxicol. 8:225-226, 1970. Abstr. 1908.
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63. Nitrosamines in food. USDA/CSRS, Exp. Sta. Letter // 1155.: 16 June
1972. pi.
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dimethylamine in smoke-processed marine fish. T. Fazio, J. N. Damio(,
J. W. Howard, R. H. White, and J. 0. Watts, Div. of Food Chem. and
Technol., Office of Foods and Nutritional Sciences, Bureau of Foods,
Pesticides, and Product Safety, PHS, DREW, Washington, D.C. Reprinted
in Ref. #28, pp 397-407.
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and creatinine. M. C. Archer, S. D. Clark, J. E. Thilly, S. R.
Tannenbaum, Science 174:1341-1342, 1971.
66. Biosynthesis of nitrosopiperidine from nitrite or nitrate and piper-
idine in the small intestine of the rat. B. S. Alam, I. B.
Saporoschetz, S. S. Epstein, Toxicol. and Appl. Pharmacol. 19:364,
1971.
67. Formation of N-nitrosopiperidine from piperidine and sodium nitrite
in the stomach and the isolated intestinal loop of the rat. B. S.
Alam et al., Nature (London) 232:116-118, 1971.
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69. Ibid., pp 250-251.
70. A survey of analytical procedures for traces of N-nitrosamines in
foods. IUPAC Tech. Rpt. # 5, Feb. 1972. Bank Court Chambers, 2/3
Pound Way, Cowley Centre, Oxford 0X4 3YF, UK.
71. Observations on the detection of dimethyl- and diethyl-nitrosamines
in foods with particular reference to alcoholic beverages. A. A.
Williams et al.. J. Sci. Food Agric. 22:431-434, 1971.
72. New view of the nitrosamine menace. Food Cosmet. Toxicol. 8:458,
1970. Abstr. 1973.
73. Toxicity of nitrosamines: their possible human health hazards.
P. N. Magee, Food Cosmet. Toxicol. 9:207-218, 1971.
74. A review of the USPHS limitation on nitrates in drinking water.
J. Van Camp. Center for the Biology of Natural Systems, Washington
University, St. Louis, Missouri, 1972.
75. The toxicology of nitrates and nitrites with particular reference
to the potability of water supplies. E. H. W. J. Burden, The Analyst
86:429-433, 1961.
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McCabe, J. Am. Waterworks Assoc. 63(2):95-98, 1971.
171
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References added in proof:
77. Methemoglobin levels in infants in an area with high nitrate water
supply. L. A. Shearer, J. R. Goldsmith, C. Young, 0. A. Kearns, and
B. R. Tamplin, Am. J. Public Health 62(9), 1174-1180, 1972.
78. Epidemiological and toxicological aspects of nitrates and nitrites in
the environment. H. I. Shural and N. Gruener, Am. J. Public Health
62, 1045-1052, 1972.
79. Nitrosation of tertiary amines and some biologic implications.
W. Lijinsky, L. Keefer, E. Conrad, and R. Van de Bogart, J. Natl.
Cancer.Inst. 49(5), 1239-1249, 1972.
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AIR POLLUTION AND HEALTH
G. J. Love
Abstract
The best Information available indicates that air pollution is a
significant factor in the production arid severity of illness. Deaths
attributable to factors possibly related to pollution have increased
significantly during the past several decades.
Disease of death occurs when environmental hostility overcomes the human
defenses. This process can be described and the effects recorded.
Community studies conducted throughout the United States by the Environ-
mental Protection Agency are documenting the associations of specific
pollution levels on the frequency of acute and chronic respiratory ill-
ness as well as the irritation of symptoms in susceptible segments of the
population, such as asthmatics, bronchitiics, or elderly individuals with
respiratory or cardiac illnesses. Recent results are reported.
Introduction
The subject of air pollution has become quite fashionable within the past
several years; but in spite of the fad, there is little agreement about
what should be controlled and the extent to which it should be controlled.
Each individual's point of view is influenced or biased by his own posi-
tion in life. Thus, we all want total elimination of pollution if
someone else is going to pay for it; on the other hand, we are more
inclined to think in terms of a reasonable level of control if the costs
are to come directly from our own pocketbooks.
Eventually, however, whatever our own personal views of the subject, the
question will arise about just how dangerous is air pollution; how many
people are affected really; and how are adverse effects produced. To
develop the answers to such questions let us consider the following few
points, many of which were lifted or paraphrased from reports of Dr.
Bertram Carnow, a well-known Chicago epidemiologist, and Dr. Patrick
Lawther, a British epidemiologist.
Our country has the highest standard of living in the world. But our
standard of health is not nearly as good. For instance, today, a 30-year-
old American man can expect to live only about two and a half months
longer than he did 30 years ago. In 16 other countries, people have
greater longevity than we have.
The diseases that are killing people in this country are cardiovascular
illnesses, bronchitis and emphysema, and lung cancer. Deaths from bron-
chitis and emphysema have increased tenfold since World War II. In a
recent year, they accounted for close to 30,000 deaths as a primary cause,
and nearly twice this many as an associated cause.
Bronchitis and emphysema are the second highest cause of disability in
Social Security recipients under the age of 65, and they cost American
173
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taxpayers more than one hundred million dollars a year in payments.
Also, emphysema and bronchitis patients have hospital stays almost twice
as long as average.
Thirty years ago, lung cancer was a rare disease. Last year, it killed
more than 50,000 men and over 10,000 women. It has been estimated that
by 1980, lung cancer will kill at least a million people a year.
Thirty years ago, cardiovascular diseases accounted for some 20% of the
deaths in this country. Last year, the figure was more than 50%.
Cardiovascular diseases killed over a million people; coronary artery
disease, usually in the form of heart attacks, killed 500,000. The
diseases that are killing people, then, are in large measure, not bacte-
rial or viral in origin; they seem to relate to events which began many
years earlier; and they seem to have more than one cause.
Now, if we have diseases that are killing people and that have long
incubation periods, it should be obvious that we had better begin doing
something about it right now; but of equal importance is the fact that
we must think in terms of prevention because many of these diseases have
very high mortality rates once they emerge as distinct entities. For
instance, almost half of the 500,000 deaths from heart attacks occurred
during the first attack, about 30,000 during the first hour.
It is now almost certain that all of these diseases have a direct rela-
tionship to air pollution. There are other causes, to be sure. There
is no question, for instance, that cigarette smoking is a major factor.
But air pollution, too, has a significant role in the causation of these
diseases.
Again referring to the reports of Dr. Carnow and Dr. Lawther, it is not
hard to accept the fact that life is a continuous struggle to adapt to
what is essentially a hostile environment—and our environment is hostile,
We fight every day to breathe, to eat, to remove waste, and to adjust our
temperature, chemistry, and body fluids. For this struggle, we are
equipped, partly at birth and partly through development, with certain
genetic, constitutional, social, and cultural defenses. If we are de-
prived of these defenses, host resistance drops. For example, cystic
fibrosis and asthma seem to make people more susceptible to lung ailments,
i.e., a child with either of these diseases is not equipped to adapt as
easily to the stresses of the environment.
Disease or death can occur either when the environment overcomes an
individual with very low resistance or when the environment becomes so
hostile that it overcomes those with even relatively high resistance.
The latter is what happened in London in 1952, when 4,000 people died in
a pollution-heavy inversion and during other major air pollution episodes.
What is more important, however, is the chronic pollution or long-time
exposure to less significant levels, which has a totally different effect.
It is known from experience that the acute pollution produces death and
worsening of disease. It is suspected very strongly that chronic pollu-
tion is responsible also for the production of disease. In general, it
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is believed to evolve in the following manner. If you irritate the lung
chronically, it will produce more mucus than is necessary, and the glands
will develop and become large and excrete masses of mucus which require
coughing and spitting to remove. Patients with this condition are said
to have bronchitis, i.e., the cough produces clear phlegm without in-
fection. There is much evidence, epidemiological and experimental, to
suggest that this picture is caused by cigarette smoking even more often
than by air pollution. In the second stage of this disease, which occurs
after repeated or continuous exposure, the secreted mucus becomes infec-
ted and then the patient begins to cough up green or yellow sputum. And
eventually, the infection begins to destroy lung tissue and to produce
emphysema. These changes are not reversible, and there is a great deal
of evidence being collected to indicate that one of the important factors
producing complicated chronic bronchitis is air pollution.
In addition, an enhancement of susceptibility to infection is associated
with irritant air pollutants. The major protective mechanism of the
tracheal-bronchial tree resides in the cilia, which beat several times
a second and escalate material out. The normal mucus blanket traps im-
purities and bacteria, and these are then swept out by the cilia. But
inhalation of relatively small doses of sulfur dioxide, nitrogen dioxide,
ozone, or the smoke from cigarettes can cause transient paralysis of
these cilia. Ultimately, after repeated or continuous stress, the cilia
and the cells containing them can be destroyed, thus eliminating the
defense and rendering the subject more susceptible to infection. The
bronchial lining is replaced in patches by different cells, which can
tolerate a lot of insult but have no ability to clear the lung. Besides,
it is thought that these cells, called squamous cells, undergo degenera-
tion and can ultimately become cancerous.
A further effect of air pollutants on respiratory defense mechanisms is
the impairment of the activity of pulmonary macrophages. These are the
cells deep in the lung, which engulf and remove foreign materials in-
cluding bacteria and other particulate matter. Inhibition of this
activity then increases susceptibility to infection and the potential
for direct tissue irritation or damage in the lower recesses of the lung.
The net effects of major .gaseous air pollutants, then, is to increase
susceptibility to acute respiratory illnesses and to chronic respiratory
illnesses such as emphysema and bronchitis, and to impair the oxygen
transfer mechanism within the lungs, thus placing a greater burden on the
heart to effectively deliver adequate quantities of oxygen throughout the
body.
Epidemiological Studies
To illustrate the extent to which at least some of these conditions are
being produced in this country, I would like to review very briefly our
program of epidemiologic studies and the results of these studies ob-
tained during the past two years.
CHESS, an acronym for Community Health and Environmental Surveillance
System, is a national program of epidemiologic studies designed to measure
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simultaneously environmental quality and sensitive health indicators
over time in sets of communities representing exposure gradients to
common air pollutants. The purpose of the CHESS program is to evaluate
existing environmental standards, to obtain health intelligence for new
standards, and to document the health benefit of air pollution control.
CHESS Area Sets. A CHESS set consists of a group of three to seven
communities selected to represent an exposure gradient for designated
pollutants. Each community within a CHESS set is a middle class residen-
tial neighborhood containing three or four elementary schools (500 to
1000 children per school) and usually a junior and senior high school.
The economic characteristics of neighborhoods are carefully matched
within the same CHESS set.
i
Each CHESS set includes high, intermediate, and low exposure communities
within which air quality varies from day to day. Health indicators are
contrasted over time and space within this framework. Replication of
pollutant exposures in several CHESS sets permits the development of
exposure-effects models in one area and the confirmations of the models
in another.
Health Indicators. CHESS health indicators focus on measures of selected
acute and chronic diseases, altered physiology and pollutant burdens.
These indicators may be conveniently divided into two categories: health
effects attributable to short-term pollutant exposure and effects at-
tributed to long-term exposure. Acute health effects are observed by
following systematically, pre-enrolled panels of subjects, and comparing
response frequency against daily variations in pollutant levels. Various
time-series analyses are employed to isolate the effects of temperature
and season on response frequency. Simultaneous observation in low
exposure communities permits the quantitatlon of the effects of environ-
mental covariates such as temperature and the detection of pollutant-
temperature interactions. These health indicators are related to
exposures of 1 to 96 hours, depending upon the nature of the response.
Effects attributable to long-term exposure are identified by contrasting
disease prevalence in high and low exposure communities. An acute effect,
such as excess acute respiratory disease, may be a manifestation of
chronically impaired resistance to disease. Persistence of illness
excess or of altered physiology in a high exposure community provides
a means to discriminate between effects attributable to short-term and
to long-term exposure. Disentangling the effects of dose-rate, that is,
large dose in short intervals vs. repeated small doses over long periods,
is difficult in community studies and generally requires controlled
experimentation.
Many factors contribute to community differences in the distribution of
diseases associated with air pollution exposure. These factors which,
along with environmental pollution, co-determine the quantitative level of
a health indicator in a community are called "covariates." Important
covarlate information obtained in the CHESS program includes age, sex,
race, education of parents, family size, occupational dust and fume ex-
posure, cigarette smoking habits, geographical migration, and previous
illness experience. Either the covariates are kept constant across study
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groups by the selection of participants, or they are measured; and then,
by proper statistical application, it is possible either to isolate or
compensate for them.
Environmental Monitoring. Air monitoring stations are sited in each
CHESS community to provide credible estimates of pollutant exposure for
the study population. The large majority of study subjects live within
1.5 miles of the monitoring station.
Manual instruments operated seven days each week monitored 24-hour inte-
graged concentrations of pollutants. Beginning last January, automated
methods listed in Table 3 were introduced into some CHESS stations, and
the entire monitoring program will be automated in 1973. Automated
stations will telemeter real time pollutant measurements to a central
processing station, providing data to relate short-term environmental
variations to health indicators of acute response.
CHESS Study Strategies. CHESS area sets are selected to evaluate exist-
ing air quality standards for particulates, sulfur oxides, nitrogen
oxides, and photochemical oxidants. Because the effects of short-term
CO exposures are more precisely studied in controlled exposure chambers,
a CHESS area set to measure CO effects was not established.
Middle class neighborhoods are chosen because they represent a large
proportion of the population and they have a more homogenous family and
social class distribution, and these characteristics change more slowly
than in central city neighborhoods.
Family participants are recruited from elementary and secondary school
enrollments in CHESS neighborhoods. Recent school busing has complicated
recruitment of families living in one neighborhood. Subjects for asthma,
cardiac and chronic respiratory disease panels are obtained from responses
to the chronic respiratory disease questionnaire and from patient listings
of private physicians. Depending on the health indicator, families and
panel members are contacted through single-time prevalence surveys,
mailed weekly diaries, bi-weekly telephone calls, or telephone calls
during episodes. Lung function of school children is measured at each
participating school; volumetric methods are employed for these surveys.
Hair samples obtained from family members are routinely analyzed for
concentrations of zinc, cadmium, lead and copper, and selectively for
other trace metals. Maternal-fetal tissue sets, including cord blood,
maternal blood, maternal hair and placental tissue, and autopsy tissues
are also obtained from each CHESS neighborhood for pollutant burden
studies. Cooperation of local hospitals is solicited for tissue collec-
tions.
It is expected that the CHESS programs will operate for three to five
years in most areas. Measurement of sensitive health indicators during
an interval of improving air quality is an optimal way to quantitate the
health benefits of pollutant controls. Studies may be extended to detect
time lags between air quality improvement and anticipated health benefit.
Development work is now in progress to deploy more sensitive and objec-
tive health indicators, particularly physiologic and biochemical responses,
of short-term variations in air quality.
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Results
The CHESS program has been in operation for a little more than two years,
and recent summaries of data have given the following results:
I. Short-term exposure
A. 365 ug/m3.S02 or more
1. Major episodes at high levels of exposure have demonstrated
that air pollution can cause increased numbers of deaths.
However, dose-response data are not obtained from these ep-
isodes and none were observed during the previous two years
in our CHESS areas.
B. Less than 365 yg/m3 S02
1. In New York City, symptom ratios for cough, chest discomfort,
and restricted activity increased during short episodes of
high S02 pollution over those occurring on low pollution days
as follows:
Symptom Ratio
S02 :
Low 104 (.04)
Pollution
High 340 ( 13)
Pollution ^°t-1J>
Episode of
<3 Days
TSP
52 Father
Mother
i Children
192 Father
Mother
Children
Chest Restricted
Cough Discomfort Activity
1.0
1.0
1.0
2.0
1.8
1.4
1.0
1.0
•1.0
6.0
7.0
6.0
1.0
1.0
1.0
11.0
10.7
2.5
Non-smokers consistently reported fewer symptoms than smokers
but were equally affected by the episode.
2. In New Cumberland, West Virginia, ashtma attacks in a group
of asthmatics increased as pollution increased:
S02 Asthma Attack Ratio
Low Exposure Day 182 (.069) or lower 1.00 (.364)*
High Exposure Day 183 (.07) or above 1.23
* Daily attack rate per person per day.
Temperature variations had the strongest effect on daily
attack rate. After temperature effects were removed, re-
sidual daily attack rates were significantly correlated;
this relationship was strongest with suspended sulfates.
Air pollution effects were strongest at moderate tempera-
tures.
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Increases in asthma attacks in New York City (143 subjects):
S02
Sulfates
(Ug/m3)
Attack
Ratio
Low Exposure Day
Intermediate
High Exposure Day'
Low Exposure Day :
Intermediate
High Exposure Day
£60 (.023)
61-80 (.p24-.029)
>80 (.03)
<8.0
8.1-12
1.00 (.213)
1.07
0.97
1.00 (.198)
1.04
1.07
4. In Salt Lake City, asthma attacks increased, as pollution in-
creased. This study included 243 children and adults:
S02
Sulfates
(yg/m3)
Attack
Ratio
Low Exposure Day
Intermediate
High Exposure Day
Low Exposure Day
Intermediate
High Exposure Day
£60 (.023)
61-80 (.024-.029)
>80 (.03)
±8.0
8.1-12
1.00 (1.48)
0.96
1.12
1.00 (1.39)
,1.10
1.16
Temperature was a highly significant covariate. Once effects
of temperature were removed, rates could be correlated with
suspended sulfates or TSP, more strongly with S02-
Without high sulfates. attack rates began to increase when
TSP was about 75 yg/m , but when suspended sulfates were
high, attack rates began to increase when TSP exceeded the
annual secondary standard (60 yg/m3).
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5. In New York City, increased irritation of symptoms occurred
in elderly panels with heart and lung disease (800 subjects
over 60 years old):
6.
Symptom Ratios
Well
Heart and
Lung Disease
Estimates
for Total
Elderly
Population
24 hr
S02
<60
60-80
>80
<60
60-80
>80
<60
60-80
>80
S02
Sulfate Suburban
<8 1.0
(7.1)
8-12 1.04
>12 1.39
<8 1.0
(19.6)
8-12 1.46
>12 1.23
<8 1.0
(7.4)
8-12 1.01
>12 1.25
Urban
1.0
(16.5)
0.96
1.12
1.0
(51.9)
0.92
1.0
1.0
(23.0)
0.98
1.06
Sulfate
Suburban
1.0
(7.3)
1.0
1.05
1.0
(17.8)
1.18
1.40
1.0
(7.5)
1.01
1.05
Urban
1.0
(14.3)
1.22
1.25
1.0
(48.7)
1.04
1.09
1.0
(20.8)
1.12
1.18
The most pronounced and consistent effects were associated
with temperature. Urban subjects appear to have had greater
initial illness.
These results confirm the fact that sensitive segments of
our population are sensitive to relatively small daily fluc-
tuations in air pollution levels.
II. Long-term exposure
A. Mortality and morbidity - exposure >120 yg/m3 annual mean
1. In New York City, non-smoking adults in high exposure areas
had chronic bronchitis rates 2.4 to 3.9 times those for non-
smokers in low exposure areas. For smokers, the relative
excess was 1.3 to 1.6 in high exposure areas:
Suburban
Urban
Urban
I
II
Annual
S02
24
175
230
(68-70)
TSP
36
80
110
Chronic Bronchitis Prevalence
Non-smokers
Female
1
(2
3
2
.0
.1)
.62
.38
Male
1
(4
3
2
.0
.7)
.89
.91
Smokers
Female
1
(10
1
1
.0
.2)
.62
.34
Male
1
(14
1
1
.0
.0)
.48
.51
180
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In Chicago, a survey of 50,000 military recruits shows that
those living in the Chicago/NW Indiana conurbation had chron-
ic bronchitis rates 10 to 21 percent higher than those coining
from outstate non-urban areas. Significantly higher rates
were found in both blacks and whites.
Pollution levels in the urban area were little above national
annual standards during the current year, but past exposure
had been significantly greater.
In Salt Lake City, chronic bronchitis prevalence among 7500
parents of elementary school children were 1.7 to 2.0 times
higher for non-smokers and about 1.4 times higher for smokers
when living in an area of higher SC>2 exposure; annual mean
108 yg/m3 (.04 ppm) and low TSP (66 ug/m3).
Chronic Bronchitis Prevalence
Annual Mean Non-smokers Smokers
S02 TSP Female Male Female Male
Clean
Areas
36
50-80
1
(3
.0
• 2)
1
(3
.0
.3)
1
(19
.0
.5)
1
(15
.0
.9)
Polluted Area 108 68 2.03 1.7 1.4 1.39
Occupationally exposed individuals were excluded from the
analysis.
4. In Montana and Idaho communities, increased chronic bronchitis
prevalence rates were observed among 4200 parents of elemen-
tary school children when annual mean 862 exposure exceeded
236 yg/m3 (.09 ppm).
Chronic Bronchitis Prevalence
Annual Mean Non-smokers Smokers
S02 TSP Female Male Female Male
Clean
Communities
Pollution
Communities
10-71 50-119
236-275 48-82
1.0
(1.2)
2.92
1.0
(1.0)
2.40
1.0 1.0
(17.0) (11.3)
1.09 1.16
A three-year study in Montana and Idaho demonstrated increased
frequency of acute LED and croup in children aged 1 to 12 com-
pared to a control group. After rates were adjusted for age,
sex, and socioeconomic factors, significant increases in the
frequency of repeated LRD and croup were found in children
who had lived in the pollution area for three years, but not
in newly arrived children.
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Annual Mean
Symptom Ratios
S02
TSP Pneumonia Croup Bronchitis
Low Exposure
High Exposure
10-80
236-275
50-112
54-102
1.0
(5.2)
1.1
1.0
(6.2)
•1.81
1.0
(14.9)
1.06
B, Morbidity - annual exposure of 80 to 120
•1. In Salt Lake City, excess acute LRD frequency was observed
in children 0 to 12 years old who had been residents for
three years or more in an area of high pollution, but not in
children with less than three years of residence.
S02
Ug/m3
Low o
Exposure
TSP
pg/m3 LRD Pneumonia Croup Bronchitis
77
1.0
(27.3)
1.0
(15.2)
One episode or more
1.0 1.0 1.0
(4.4) (16.9) (16.5)
Two or more episodes
1.0 1.0 1.0
(1.2) (8.0) (6.5)
High
Exposure
108 68 One-episode or more
1.4 1.09 1.56 1.53
Two or more episodes
1.54 1.0 1.73 1.66
2. In Chicago, members of volunteer families experienced a 30
to 50 percent excess frequency of acute LRD in the higher
SC>2 area. (106 pgS02/m3 - high exposure, 57-ug/m3 - low
exposure)
C. Morbidity -• exposures of less than 80 pg/m3
1. In New York City, members of families experienced a 20 to
40 percent excess frequency of acute LRD in the higher
exposure areas. Additionally, these families experienced
increased severity of their LRD.
182
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Annual Relative Risk of Acute
Low
Exposure
High
Exposure
S02
23
50-88
Pre-school
TSP Children
34 1.0
(4.59)
87-104 1.42
School
Children
1.0
(3.51)
1.21
Mothers
1.0
(2.28)
• 1.23
LRD
Fathers
1.0
(1.80)
1.24
Parental smoking was associated with increased frequency of
LRD and severity of LRD in children. Gas used for cooking
or in space heating was associated with increased severity
but not increased frequency in mothers and children.
2. In New York City, ventilatory function was decreased in
children 9 to 13 years old who had experienced high pollu-
tion during the period of their rapid lung development.
Function ranged 2.4 percent below that of children from less
polluted areas.
3. In Cincinnati, ventilatory function was decreased in chil-
dren 7 to 8 years old living in the high pollution exposure
areas. In this study, function was decreased about 15 per-
cent and was associated with suspended sulfate concentrations.
Conclusion
The significance of these studies is obvious. They confirm the fact that
higher rates of acute and chronic illnesses are associated with moderate
increases in pollution. It is not possible at this time to attribute all
of this excess illness to present levels of pollution since the effects
of prior exposure are unknown. However, the current studies amply support
the levels established as ambient air quality standards.
References
1. Carnow, B. 1971. Air pollution invites disease. Bull. Natl. Tuber-
culosis and Respiratory Disease Assoc. 57(8):.7-10.
2. Lawther, P. 1970. Some recent topics in air pollution and health in
London. J. Japan Soc. Air Pollution 4(3):223-230....
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TERATOGENESIS AND MUTAGENESIS OF ENVIRONMENTAL CHEMICALS
Hans L. Falk
If a discussion of the carcinogenic potential and the threats to man's
health by environmental chemicals is full of ambiguities, the situation
regarding mutagenic and teratogenic hazards is even more complicated..
I should like to start with separation of mutagenesis and teratogenesis,
two hazards often mentioned in one breath but which involve different
mechanisms and usually relate to different types of chemicals. They
are always bunched together under the heading of human birth defects
because it may be impossible to identify the mechanism involved without
further study.
Environmental Chemicals as Teratogens
The problem of teratogenesis has been brought to everyone's attention
following the publication of the studies on 2,4,5-T and its follow-up,
which I shall mention to point out some of the difficulties which have
been encountered. This compound was tested as one of a group of pesti-
cides without any anticipation of health hazards or suspicion. The
commercially available product was chosen for the study. Because of
extensive use of the herbicide—in 1964 in the U.S., 1.5 million pounds
were used on farms and 7.3 million pounds were for non-farm use, mostly
for right-of-ways, a total of nearly 9 million pounds—it was felt to
be of importance to study its potential toxicity.
At the time the studies were initiated, the use of 2,4,5-T in formula-
tions for military defoliation in Vietnam was not general knowledge and
it was used to a very minor extent. The herbicide was used in the U.S.,
as permitted by USDA regulation, on apples, blueberries, cereal grains,
sugar cane, rangeland, lakes and ponds.
One difficulty in its identification was the non-specific description of
the products as 2,4,5-T when it was used as the acid, as a salt, or as a
variety of esters. It was realized that this could cause complications,
but not the complication actually encountered. As it was assumed that
the acid would be less toxic than some of the esters, it was used in
that study. It was tested in two strains of mice at three dose levels
and administered, orally or by subcutaneous injection, during days 6-14
or 9-17 in C57 black mice, or on days 6-15 in AKR mice. The results
showed statistically significant increases in cleft palates and cystic
kidneys in the fetuses.
Because of the positive results in mice, tests were also carried out on
Sprague-Dawley rats given orally at three dose levels from 4.6 to 46.4
mg/kg from day 10-15 resulting in cystic kidneys in these fetuses. The
highest dose administered produced fetal mortality so that inadequate
information on .malformations was obtained in that group. Very striking
was the observation of hemorrhages in the gastro-intestinal tract of rat
fetuses which showed a dose-response relationship. It was of interest
that 2,4-D did not produce similar teratologic effects; only some of the
esters showed weakly positive results.
185
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At this stage, industry helped to clarify the situation by analyzing the
sample of 2,4,5-T that had been used for these studies and detecting
contamination of the sample with a highly toxic compound, 2,3,7,8-
tetrachlorodibenzo-p-dioxin. This compound had in the past been held
responsible for the production of chloracne in a number of workers
involved in the synthesis of 2,4,5-T, particularly in the cleaning
operations of apparatus. Following this discovery, the process of
2,4,5-T synthesis was altered slightly so as to avoid the production
of the dioxins. This discovery was made and remedial action taken after
the samples for these studies had been obtained, and the investigators
were not aware of the contaminant or its partly known toxicity.
With this information and the collaboration by industry, the impurity
was obtained for study, as was technical 2,4,5-T of recent vintage and
a particularly pure sample of the herbicide without detectable dioxin
contamination. Other impurities present in commercial 2,4,5-T were!also
identified.
The results of these follow-up studies were very interesting. The
increased incidence of defects and fetal mortality in the rat could be
blamed entirely on the impurity (the dioxin). The hemorrhagic GI tract
in mice was also caused by the impurity. However, even the highly puri-
fied 2,4,5-T still produced cleft palates and renal defects in mice.
The dose required, however, was very high: 100 mg/kg subcutaneously in
DMSO as solvent given to Charles River mice from day 6-15 of pregnancy.
In contrast, kidney involvement was seen with dioxin at the 1 yg/kg
dose level in the same experimental setup.
These studies seem to have come to a successful conclusion; namely, the
identification of a very toxic impurity which has, for other reasons,
already been eliminated from the present-day 2,4,5-T herbicide, leaving
the product, if not completely clean, at least of negligible toxicity.
However, a survey made recently of a number of pesticides by USDA scien-
tists revealed that several pesticides derived from chlorinated phenols
contained sizeable amounts of various chlorinated dibenzo-p-dioxins.
Thus, samples of pentachlorophenol had high levels of octa- and hepta-
chlorodibenzo-p-dibxins with lower amounts of hexachloro and fewer
chlorinated dioxins in 10 out of 11 samples. The dioxin levels were
very high, between 10 and 1000 ppm of the higher chlorinated dioxins.
The samples of tetra- and trichlorophenol tested were far lower in
dioxins.
In recent times, the contamination of PCB's with chlorinated dibenzo-
furans and dioxins in Europe and the U.S. has been documented so that
the problem has not disappeared as yet. However, much greater emphasis
has been placed on the hazards of this type of contamination, so that
it will be looked for and eliminated. The possibility that new anti-
bacterials may contain or give rise to dioxins must be taken into
consideration when hexachlorophene will have to be replaced by other
antibacterials.
Although enough information appears to be available on the rates of
degradation of 2,4,5-T herbicides, little information exists for dioxin
degradation, except for one report on photodecomposition of chlorinated
186
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dibenzodioxins. Iri this study, decomposition on exposure to ultraviolet
light or sunlight was observed in vitro on solution of the dioxin in
alcohol, but no such luck was had when the material was present in
aqueous suspension or in soil.
The hazard that may arise when chlorinated phenols on herbicides like
2,4,5—T are exposed to conditions that may cause their transformation to
dioxins must be carefully evaluated. Such a hazard may not depend on
the optimal pH for dioxin formation but could be present on pyrolysis
of large quantities of the herbicide even though at a very low yield.
The considerable attention paid to 2,4,5-T as a potential teratogen has
resulted in ignorance of other environmental chemicals that may have
similar ^oxicologic properties. In the large scale screening which
detected -the herbicide 2,4,5-T as teratogenic, some others were also
found to be. active, particularly pentachloronitrobenzene (PCNB). PCNB
produced renal agenesis in C57 black mice when administered from day
6-10 of pregnancy at 460 mg/kg; when administered from day 10-14, this
effect was not observed.
Savin, Captan, and Folpet were also found to be teratogenic to, some
extent, but less strikingly so, even though the appearance-"bf abnormal-
ities was statistically significant. Many other insecticides, among
them the chlorinated hydrocarbons and the organophosphates, were also"
teratogenic in a number of test species. So were mercury compounds,
including methylmercury. ,..-.- ' -"""
Toxic chemicals which the mammalian organism has little capacity to
excrete or detoxify in its organs and tissues may turn out to be terato-
genic. Under conditions where detoxification and elimination are
prevented, the transfer from the mother to the developing fetus is one
of the only routes of elimination of the chemical. Experimental data
on teratogenesis exists for such chemicals, i.e., mirex, the chlorinated
dibenzo-p-dioxins, the polychlorinated biphenyls (PCB's), and methyl-
mercury. It will be true for other environmental chemicals which are
lipid soluble and hard to detoxify and conjugate.
When reviewing the literature, including the Report of the Secretary's
Commission on Pesticides and Their Relationship to Environmental Health,
one becomes concerned about the potential teratogenicity of many envi-
ronmental chemicals. This is particularly true when the chick embryo is
chosen as the test animal. Criticisms have been raised against the use
of that species because the introduction of any foreign chemical is
final. Unlike the mammalian fetus, the chick embryo cannot eliminate
the chemical successfully. The choice of a mammalian species circum-
vents that situation and makes the experiments more extrapolatable.
After an early "successful" attempt to duplicate the teratogenicity of
thalidomide in the chick embryo, one investigator replaced the insoluble
drug by 'an equivalent number of grains of sand and produced the same
teratogenic effects. However, even in the case of soluble chemicals,
the chick can o'nly serve as a simple screening test for chemicals with-
out immediate follow-up by legislative action.
187
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Considerable efforts are being made to come up with adequate test
systems. The results obtained with 2,4,5-T serve to illuminate some
problems quite clearly. Besides the purity of the compound, the choice
of species and strain is important. The data on the rat, which are
negative, can be contrasted with those on the mouse, which are positive;
further studies may determine if mouse or rat is closer to man.
Sometimes the ability to eliminate the compound through the kidney is
the crucial event; in other situations, it is the binding to plasma pro-
teins that may make the difference in toxicity. Thus, it is important
to determine some of the pharmacologic parameters for experimental
animal species and for man before carrying out too many experiments
and blindly using too many species or strains. However,-it must be
recognized that, within a species, the physiologic, pharmacologic, or
biochemical characteristics of the adult may differ significantly from
those of the fetus. I
One of the problems deals with the timing of the chemical insults. The
mouse and rat have a very short organogenesis time which does not allow
for very careful pinpointing of the time of the actual interaction.
These species are, therefore, very useful for quick answers on potential
teratogenic hazards. However, they are less suitable to answer questions
on specific times during pregnancy which may be more or less sensitive
to chemical insults. Therefore, there is a need for additional studies,
once a chemical has been found to be teratogenic to mice or rats, with
species with longer pregnancies to determine the sensitive period for
better extrapolation to man.
Evidence of human teratogenicity due to environmental chemicals is quite
sparse and particularly inconclusive regarding the effects of chlorinated
hydrocarbon insecticides or organophosphates. High dose exposure to
PCB's and methylmercury, on the other hand, shows the teratogenic effect
of these chemicals taken with the food. From such data, it was possible
to determine intake levels that were without effect on the developing
offspring.
One can conclude that teratogenic effects in humans have not been
observed unless, the intake of the environmental chemical was exceedingly
high. Among these environmental chemicals, one encounters some that
resist degradation in the environment or in the mammalian organisms and
that accumulate in tissue and will reach the developing fetus transpla-
centally or the young infant through his mother's milk. A few toxic
chemicals fall into this classification, and introduction of these
chemicals into man's environment must be avoided by all means.
Environmental Chemicals as Mutagens
Mutagenic chemicals in man's environment may represent the most serious
health hazard. They deserve attention of the highest priority before
the ill—effects may become apparent in future generations when no reme-
dial steps may be available to turn the clock back. It is not at all
certain that we have already encountered such a situation of exposure to
mutagenic chemicals, but this situation may arise at any time, if it has
not happened yet.
188
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A consideration of mutagenic hazards for man must take into account all
factors possibly involved in producing this hazard for man and cannot
rely on evidence only that the chemical possesses mutagenic properties
for some microbial test system. The test systems that have been used in
the past and that are still in use today are very sophisticated, but they
are limited in application when extrapolation to man is required. Sys-
tems that determine effects on bacteria, fungi, viruses or mammalian
cells in tissue culture suffer from shortcomings relating to the lack
of potential barriers between the chemical and the genetic material,
which is quite complicated in the mammalian species. Conditions also
differ with regard to the defense systems available in the mammalian
organism which are at work and may completely alter the hazard. On the
other hand, certain chemicals which become activated to mutagenic com-
pounds by mammalian metabolic steps would not give evidence for muta-
genicity in the above-mentioned systems.
The simple systems mentioned above nonetheless serve their purpose;
namely, to differentiate between mutagenic chemicals that are effective
without metabolism and those that need activation, which are not detected
in these simple tests. Their main purpose, of course, is to have a first
screen. If the result is negative, it does not allow immediate approval
of the chemical for large scale use; and if positive, it similarly does
not suggest legal action as the next step without any further testing.
Looking at pesticides, for example, it is apparent that use is made of
some chemicals on the basis of their mutagenic properties. We would,
therefore, have to conclude on the basis of microbial tests that these
chemicals must be removed. Chemosterilants, which are used together
with ultraviolet light, insect pheromones or other attractants for insect
control, will kill, sterilize or cause genetic damage. The compounds
have been studied exhaustively and qualify as potent mutagens. The
question, therefore, is whether, under the conditions of usage, a hazard
may exist for man and other species. The chemosterilants are highly
toxic chemicals also for man. However, they tend to break down and the
rate of degradation has been determined which showed that, although the
parent compound was readily degraded, alkylating activity was still
present in the insect after some time. The activity was due to ethylene
imine, a breakdown product of the chemosterilant. As the insect may
serve as food for other animals, it is possible that some hazard may be
transmitted to the predator, be it a fish or a bird; but it is not likely
to reach man through the food chain under most conditions.
Other pesticides, particularly the herbicides, may exert their function
by interfering with cell replication. Results show the appearance of
chromosomal breaks in many plants where exposed to herbicides. The
herbicide may at first still be in its active form in the plant, although
its metabolism in the plant tissue will lead to its inactivation. When
it remains intact, as in the case of maleic hydrazide, it could present
a hazard to man in some food staples. However, the amount of the com-
pound used and the residues encountered in food staples are rather
insignificant.
189
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Fungicides also proved mutagenic, and the list of potential mutagenic
chemicals among the pesticides is large. This high probability cannot
be applied across the board to other groups of environmental chemicals,
because the chemicals selected for pesticidal use were, of course,
lethal to the organisms to be controlled, frequently affecting their
reproductive capabilities.
For each of the pesticides, additional studies are needed to determine
whether the mutagenic effect will reach man on environmental exposure
to the chemical, as contrasted with occupational exposure.
Fortunately, many investigators have asked relevent questions and found
answers, so that we can evaluate the probability of these chemicals
reaching man intact to present a mutagenic hazard. Pesticides as the
fumigants are very reactive and will not be mutagenic after they have
reacted. Acrylonitrile, hydrogen cyanide, formaldehyde, ethylene oxide,
betapropiolactone, methyl bromide, and methylene bromide belong to this
group. The reactivity of these chemicals does not, however, imply that
there is no health hazard; although the mutagenic property is lost, the
reaction products may be toxic.
The same situation applies to fungicides such as Captan or the metallo-
dithiocarbamates which readily decompose and thus represent less of a
mutagenic hazard. Other fungicides, such as methylmercury, however,
maintain their toxicity. In general, every pesticide has to be studied
separately to determine the reactivity of the compound in its ecologic
system and the rate of degradation in mammals if it reaches them in the
food chain.
Once the chemical has been ingested, it is not certain that it will
reach testes or ovaries; and it has been documented that the chemical
does not cross the barrier that easily; so an extrapolation from the
microbiological or mammalian in vitro system is not justifiable.
However, among the chemicals that represent a potential hazard, the most
problematic ones are those that are not very reactive and may have a
considerable biologic half-life, and those that are precursors of muta-
genic compounds and require metabolism before being activated. These
compounds may play havoc in mammals, yet would not be detected in the
general test systems mentioned before. Adequate test systems required
for their detection are being developed and will soon be available.
In order to respond to this need, the host-mediated assay was developed
which introduced into mice the microorganism and the potential mutagen
which may require activation by the mammalian organism.
A few problems remained with the host-mediated assay, however. First
was the problem that the host did not take kindly to the invasion by
microorganisms and by mobilization of macrophages would soon annihilate
the microorganisms. The time for the experiments was, therefore, lim-
ited; and the conditions for survival of the cells were not good. A
second problem was the need for metabolites to become available to the
microorganisms; and the possibility exists that metabolism was too slow,
190
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.that metabolites would be further modified, i.e., conjugated or elimi-
nated by the kidney, giving the impression that no mutagenic compounds
were formed. Tests could be negative also if the compound was excreted
in the bile to be reabsorbed into the circulation after hydrolysis,
bypassing the peritoneal cavity and its occupants. Its mutagenicity
would be missed.
The newly developed host-mediated assay utilizing mouse cells introduced
into the murine peritoneal cavity in a semipermeable chamber will take
care of some of the problems; however, the body's defenses may close off
the membrane, so that after awhile the metabolized chemical, if present
in the peritoneal cavity, may not reach the cells.
'When considering the number of chemicals that possess mutagenic proper-
ties, we must realize that the organism possesses defense mechanisms
that are fast at work to repair the damage to DNA. It is not the excep-
tion but the rule that damage to DNA by crosslinking or single hits is
rapidly detected and repaired by enzymes which have several mechanisms
at their disposal to excise the damaged parts and to repair them. The
repair of ultraviolet-damaged DNA (formation of thymine dimers) has been
examined and the enzymes involved have been characterized. In organisms
in which these repair enzymes are absent, damage may be permanent and
lethality and mutagenesis are much enhanced. Similarly, in humans
suffering from xeroderma pigmentosum, the repair enzymes are deficient
and cells from the skin of those patients demonstrate lack of excision
of dimers and lack of appearance of short chains of DNA, which are
normally formed during repair and disappear when normal cell repair is
completed.
If we are reassured that for most humans this risk of missing repair
mechanisms does not exist and that other repair mechanisms actually exist
in addition, it comes as a shock that synergism has been observed, i.e.,
a. greater mutagenic risk when certain chemicals are introduced which will
interfere with repair mechanisms. So far, only a few chemicals have been
found to interfere with the repair mechanisms, but only very few have so
far been tested.
It seems clear that a search for mutagenic chemicals in the environment
must be initiated so that we will know which chemicals might present
potential risks. However, after this primary screen, we must determine
the probability that the chemical could reach the target tissue in a
high enough dose to be an effective mutagen. It is not true that one
molecule would be sufficient to cause a mutation considering side
reactions with other molecules, metabolism and detoxification of the
mutagen, and the varieties of cells that may be hit by the mutagen. Even
if the "proper cell" in the "proper stage" has been affected and the
result is a point mutation, it is not at all certain that the DNA strand
which has been hit is part of an active gene, or that the base is in a
crucial position where change will alter the translation of the code, or
that the replacement of the amino acid by a different one will produce
changes that are functionally important, or that the mutation will not
be repaired.
191
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On the other hand, if the mutation is carried along, and even if it is
only of minor importance, it may persist without producing any lethality;
and many may accumulate as recessive mutations until the load of these
multiple minor modifications leads to true deficiencies and difficulties
in future generations.
We need to perfect test systems, to initiate screens, and to initiate
all the other biochemical and physiologic studies to determine the
biologic half-life and the chances of receiving a load of undesirable
genetic traits; and we must take action to eliminate! the hazardous
chemicals from common use.
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PESTICIDES IN AIR
Lawrence M. Mounce
Pesticides are one of several classes of toxicants which are present in
our atmosphere. This class of toxicants is in contrast with some of
the domestic and industrial contaminants which merely add to compounds
naturally occurring in air. Pesticides, which are generally regarded
as those synthetic chemicals having been produced since World War II
and used as insecticides, herbicides, and fungicides, are original air
pollution burdens which can alter the quality of air.
Air is one of the three main reservoirs for pesticide residues with the
other two being soil and water. Much investigational and monitoring
work on pesticides in soil and water as well as vegetation, wildlife,
and humans has already been conducted; however, much less knowledge has
been accumulated on the incidence and levels of pesticides in air.
This is in part due to the small sample sizes available because of the
great volume and dilution factor of air, and partly due to the lack of
adequate sampling and analytical methods. Despite these limitations,
there is an increasing body of data to indicate the universal presence
of pesticides in air. The significance of these airborne pesticides to
man, the environment, and the ecosystem is less clear.
Three important reports on the subject of pesticides were prepared by
national committees or commissions and released in the year of 1969.
Significant statements relating to pesticides in air from these reports
are as follows:
1. The report of the Committee on Persistent Pesticides of
the National Research Council dated May 1969 states the
following: "Although the technology of air sampling is
not well advanced, air sampling must be included in any t
effort whose aim is to monitor the health-related aspects
of man's immediate environment. Further, the absence of
quantitated information about transport of pesticides in
the atmosphere is a critical deficiency in our understand-
ing of the biosphere circulation of persistent materials."
2. The report "Cleaning Our Environment: The Chemical Basis
for Action: by the American Chemical Society lists the
following recommendations:
"P-l: Pesticide Monitoring Programs on all phases
of the environment should be continued. In
the case of air...the present programs should
be extended."
"P-2: For purposes of chemical analysis, research
should be pursued oh the development of more
adequate methods for the separation of minute
amounts of pesticides from water and air."
"P-3: Research should be expanded on the toxicity
of pesticides when they are inhaled as op-
posed to dermal exposure or oral intake."
193
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3. The report of the Secretary's Commission on Pesticides
presented 14 broad recommendations. One of these reads
as follows: "Develop suitable standards for pesticide
content in food, water and air..."
I believe these conclusions and recommendations point out the unknowns,
problems, and challenges with respect to pesticides in air.
Not only are pesticides originally-occurring foreign substances in air,
but they are also intentionally injected through the air to crops and
other target objects, whereas most other airborne contaminants are
incidental to transportation or the production of power.
Pesticides may enter the air in several ways. These are:
1. Drift and volatilization from aerial or ground applica-
tions.
2. Volatilization from treated soil, plants, or water.
3. Wind translocation of particulate matter such as soil and
plant fibers.
4. Domestic use of aerosols and thermal vapors incidental to
the production and formulation of pesticides.
Drift. One of the first and probably the most familiar problem relating
to airborne pesticides is the occurrence of drift from the target crop
to non-target areas. The application that obliterated the cucumber
patch as well as the weeds in the adjacent wheat field, and the wither-
ing flower bed adjacent to the neighbor's weed-free lawn are familiar
stories. Such economic and aesthetic effects are immediately apparent.
On the other hand, drift onto non-target food crops may not be visually
apparent but has been an avenue of chemicals entering the food chain
and had resulted in the seizure and condemnation of human and animal
food crops. After World War II, crop dusting, both aerially and with
ground rigs, was a common practice; but now the term "cropduster" is
becoming a misnomer as it is becoming hard to find an applicating firm
that will apply a chemical in dust form. This is indicative of the
greater drift problems associated with dust application and the greatly
increased ability of chemists. Crop dusting has given way to spraying.
Refinements in the design of agricultural aircraft, better control of
the spray through calibration of particle size, and improved formulations
of chemicals have all contributed to reducing the problems associated
with drift. Newer forms of application, such as the use of granules and
foam, show promise for further reducing drift and the contribution of
pesticides into the air. •
Many studies have been made concerning the factors involved in drift.
One of these studies has shown the difference in drift between a spray
and a dust application. DDT was applied to a field and its concentra-
tion was then measured one-half mile downwind. The dust concentration
was 1.4 ppm, whereas the concentration from the spray was only 0.1 ppm.
This and other studies have shown that drift is related to particle size,
with the sprays being in the 150-200 y range and dust being in the 10-20
y range.
194
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Volatilization. Volatilization of pesticides from treated soils, plants,
and water is dependent on complex interrelationships involving properties
of the chemical, the soil, and the climate. Chemical properties which
are important include acqueous solubility, vapor pressure, and the
intrinsic stability of the compound. The absolute vapor pressures of
the organochlorine insecticides are very low, yet volatilization is one
of the most important causes of loss from the soil, and this is enhanced
in the presence of free water at the soil surface. Vaporization is a
continuous process throughout most of the year; and the rate of release
will depend upon such factors as temperature, soil tillage, type of crop
cover, and similar factors.
Translocation. In 1966, Cohen and Pinkerton (2) reported the transport
of pesticide-laden dust through the atmosphere. This dust originated
in a mammoth dust storm over the Southern High Plains west of Lubbock,
texas, and was subsequently deposited by rainfall many hundreds of miles
away 24 hours later. Results of analysis are given in Table 1.
TABLE 1 (2)
Pesticide Content of Dust
Pesticide Concentration (ppm)1
DDT (tech.) 0.6
Chlordan (tech.) 0.5
DDE 0.2
Ronnel 0.2
Heptachlor epoxide 0.04
2,4,5-T 0.04
Dieldrin 0.003
Total organic chlorine 1.34
Total organic sulfur 0.5
1 Based on air-dried weight of dust.
Pesticides or related products may be discharged directly into the air
through smokes and other clouds incidental to manufacturing or proces-
sing or in burning of "empty" containers, or even in the case of fires
in warehouses and such situations. Wolfe et^ al. (10) have reported
finding as much as 7.9 mg/m3 of parathion in such smoke.
The distribution and dispersion of airborne pesticides will depend on
particle size and meteorological conditions as well as distance above
ground at which they become airborne. Information on the dispersal and
distribution of pesticides in the vapor phase or in the particle range
below 5 y is almost completely lacking.
195
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The Division.of Pesticide Community Studies of the Etivironmentar Protec-
tion Agency has been, conducting a monitoring program for the. past two
years to determine the incidence and levels', of pesticides in the air on
a national basis. This is known as the Air Monitoring Program and .is
under the direction of: Dr. Anne Yobs. This program has collected 1,850
samples over a two-year period from 45 sites throughput the contiguous
48 states with ..one sampling site in the Bahamas. I consider this to be
the most comprehensive air sampling program for pesticides. '
One of these sites is located at the Colorado Project in Greeley. The
type of sampler used is one which was developed by the Midwest Research
Institute and is of the impinger type whereby air is bubbled through
ethylene glycol trapping both particulates and gases. The results show
that DDT and one of its metabolites, Dieidrin, and two ispmers of BHC
were found in more than half the samples. Two isomers of DDT and
Dieidrin were found at all sites last year. You may note that all these
compounds mentioned are in the more persistent class of chlorinated
hydrocarbons. Other pesticide chemicals have been detected in the
chlorinated hydrocarbon group as well as organophosphate pesticides,
but with less frequency. These results are found in Table 3 (13).
The national levels do not approach the American Congress of Governmental
Industrial Hygienists' threshold limits. A wider variety, although not
the highest levels, of pesticides have been found in the urban and com-
mercial areas as compared to residential, agricultural, or rural areas
(Table 2). :
TABLE 2 (13)
Average Number of Pesticides Reported by Land Use .
Urban commercial
Rural farm
Urban residential
Urban agricultural
Rural non-farm
1970
13.2
11.0
10.8
10.0
1971
' 12.3
12.0
11.0
10.2
8.2
The Colorado Project, in addition to the air monitoring work, has pur-
sued the subject of pesticides in air from a slightly different approach.
Prior work at our project with three groups of families '(an urban con-^
trdl, rural and pesticide-exposed worker .family groups) involved the
analysis of environmental samples such as soil, water, housedust, and
diet as well as blood samples from these groups. Housedust was the only
variable showing any association to blood residues of the family members
from two sets of such data. This suggested an environmental influence
and the possibility of residue deposition in housedust from the air
seemed strong. .
196
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TABLE 3 (13)
Incidence of Pesticides in Ambient Air, 1971
Pesticide
p,p'-DDT
p,p'-DDE
Dieldrin
o.p'-DDT
a-BHC
S-BHC
Heptachlor
8-BHC
Endrin
p,p'-DDD
Toxaphene
Treflan
Chlordane & metabolites
Dae thai
Thiodan
Aldrin
o,p'-DDE
o,p'-DDD
Captan
Methoxychlor
Kepone
Diazinon
Malathion
M. Parathion
Phorate
Parathion
Phosvel
Mocap
Ronnel
Ethion
Trithion
Folex
2,4-D esters
2,4,5-T esters
Azodrin
No. Times
Reported
936
900
842
769
678
563
265
108
108
98
72
53
47
23
19
17
7
6
6
5
3
318
136
54
41
26
11
5
3
1
1
1
122
25
4
Percent
Samples
Positive
96.7
93.0
87.0
79.4
70.0
58.2
27.4
11.2
11.2
10.1
7.4
5.5
4.9
2.4
2.0
1.8
0.7
0.6
0.6
0.5
0.3
32.9
14.0
5.6
4.2
2.7
1.1
0.5
0.3
0.1
0.1
0.1
12.6
2.6
0.4
No. Sites
Reporting
45
43
44
42
27
24
17
12
6
15
4
8
10
2
5
3
1
1
3
1
1
24
19
8
7
9
1
1
1
1
1
1
13
6
1
Total Sites: 45
Total Samples: 968
197
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This was followed by a year-long study involving inside and outside air
samples and housedust samples collected monthly from 12 homes of farmers
and pesticide workers. More compounds were detected in the inside air
samples than in the outside air samples, and the levels were also gen-
erally higher. High housedust and inside air residue levels were also
associated (Table 4).
Impact
Factors to be considered in the assessment of pesticides in the atmos-
phere include:
1. With air being the most fluid of the reservoirs, pesti-
cides are more easily and rapidly dispersed.
2. Dispersion into the air reservoir is also the most diffi-
cult to control.
3. Pesticides are present, however minute, in the atmosphere
and in the air we breathe.
4. The function of respiration is designed for the efficient
absorption or exchange of the gases in the air we breathe.
It is a continuous and intimate contact. The lungs utilize
about 10,000 liters per day; the surface area of the lungs
is 80-100 square meters as compared with our body surface
of about 1.73 square meters.
5. The potential for reacting with other air pollutants,
conversion to other toxic forms, or the production of
other compounds must be considered.
198
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• TABLE 4 (13)
Percent Incidence of Pesticides in Environmental
Samples from Homes of Pesticide Workers
Pesticide
Organochlorides
p,p'-DDT
p,p'-DDE
o,p'-DDT
p,p'-DDD
Methoxychlor
a-BHC
Lindane
Chlordane
Heptachlor
Heptachlor epoxide
Dieldrin
Endrin
Endosulfan
Herbicides
Dae thai
Organophosphates
Parathion
Methyl parathion
Diazinon
Ronnel
Ethion
Outside Air
100
100
99
16
24
100
79
95
3
11
99
75
5
85
55
6
8
18
0
Inside Air
100
99
100
26
11
44
89
74
4
1
99
64
19
90
65
16
15
9
14
Housedust
99
22
48
8
15
0
18
56
0
0
33
10
14
48
57
27
30
26
19
Number of Samples: 149
199
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References
1. American Chemical Society. 1969. Cleaning our Environment: the
Chemical Basis for Action. A report by the Subcommittee on Envi-
ronmental Improvement, Committee on Chemistry and Public Affairs.
2. Cohen, J. M. and Pinkerton, C. 1966. Widespread translocatipn of
pesticides by air transport and rain-out. Organic Pesticides in
the Environment, Advances in Chemistry Series: 60.
3. Freed, V. H. 1970. In J. W. Gillette, Ed., The Biological Impact
of Pesticides in the Environment. Environmental Health Sciences
Series No. 1, Corvallis, Oregon.
4. Handbook of Analytical Toxicology. 1969. I. Sunshine, Ed. The
Chemical Rubber Co., Cleveland, Ohio.
5. Jegier, Z. June 23, 1969. Pesticide residues in the atmosphere.
Ann. N.Y. Acad. Sci. 160:1.
6. Middleton, J. T. 1960. Research in Pesticides. Academic Press,
New York.
7. National Research Council to U.S.D.A. May 1969. Report of the
Committee on Persistent Pesticides, Division of Biology and
Agriculture.
8. Tessari, J. D. and D. L. Spencer. November 1971. Air sampling for
pesticides in the human environment. J.A.O.A.C. 54:6.
9. U.S. Department of Health, Education, and Welfare. December 1969.
Report of the Secretary's Commission on Pesticides and Their
Relationship to Environmental Health. Parts I & II. E. M. Mrak,
Chairman.
10. Wolfe, H. R., W. F. Durham, K. C. Walker, and J. F. Armstrong.
November 1961. Health hazards of discarded pesticide containers.
Arch. Environ. Health 3:531-537.
11. Woodwell, G. M. March 1967. Toxic substances and ecological
cycles. Sci. Am. 216:3.
12. Yobs, A. R. January 1971. Pesticides in air. Proceedings of the
Training Course: Pesticides and Public Health Advanced. Pesti-
cides Office, E.P.A.
13. Yobs, A. R., J. A. Hanan, B. L. Stevenson, J. J. Boland, and
H. F. Enos. April 11, 1972. Levels of selected pesticides in
ambient air of the United States. Symposium on Pesticides in Air,
National American Chemical Society, Boston.
200
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Operations Division, Office of Pesticide Programs
CHAMBLEE, GEORGIA 30341
April 30, 1973
MAY 14 1973
PESTICIDES LIBRARY
TO ALL COURSE PARTICIPANTS:
The paper entitled "The Effects of Environmental Impact
Statements on Federal Pesticide Programs" by William M. Hoffman
was omitted inadvertently from the proceedings of the course,
__ "Environmental Chemicals - Human andJ\fljjiia1^Health.'' We regret
this omission and enclose a copy of the paper, which may be
inserted in your copy of the book following page 200.
Sincerely yours,
/ ' l-'M. -*— / \ ' '
/ Anne R. YabsJ-M.D.j
Chief, Training &
Enclosure
ucation Branch
/
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THE EFFECT OF ENVIRONMENTAL IMPACT STATEMENTS
•"•"'•' ON' FEDERAL PESTICIDE: PROGRAMS*
William M. Hoffman
Senior'Advisor, Office of Pesticides Programs .
Environmental Protection Agency ; ??••••
Washington, D.C. 20460
"'.*-!' '' ' ' •' ,; ' '•, ' • • ' ." " ' '"'.*; ' ' ' ' •' •"'-.•'.'•
; •.-';,••., , '.. . jr _ ...... . .--. - . ........
President Richard M. Nixon symbolically chpse to sign as his first offi-
cial act of the decade of the Seventies 'the" National Environmental Policy
Act of 1970 (NEPA). :At thei time it was hailed as "one of the most sig-
''nificant"'"and "the most important and far-reaching conservation measure
ever enacted." Now, some 2-1/2 years later, the Act has established-it-
self as ;one of the most controversial environmental measures of all times--
one whose impact has touched virtually every department of the Federal
government and many a Member of Congress in a very short time.-
The Purposes of the Act
To declare a national policy which will encourage productive and enjoyable
harmony between man and:his^environment, and to establish a Council on
Environmental Quality (CEQJ. The Administration originally proposed a
cabinet-level coordinating ctimmittee but Congress insisted on a statutory
council and so CEQ was created as a three-member body appointed by the
President and subject to Senate confirmation. By law, CEQ is authorized
to: • ' • '
1. Assist the President in preparing the annual environmental quality
report.
2. Gather information on'environmental conditions and trends.
3. Review and appraise Federal activities affecting the environment.
4. Develop ahd recommend environmental policy to the President.
5. Conduct ecological and environmental investigations and research,
and
6. Conduct such other studies as the President may request.
When the executive order directing implementation of the procedures of
the Act was passed, CEQ was given further authorization to:
*Presented at the course "Environmental Chemicals - Human^:and Animal
Health," sponsored by the Institute of Rural Environmental Health,
Colorado State University and Division of Pesticide Community Studies,
EPA, August 7-11, 1972, Fort Collins, Colorado.
200a
-------
1. Conduct public hearings and conferences on environmental issues.
2. Coordinate (not merely review and appraise) Federal activities
affecting the environment.
3. Issue guidelines to the Federal agencies for compliance with
the Act, and
4. Issue such other instructions to the agencies and request such
information from them as necessary to fulfill its responsibilities.
The significance of these added authorities is evident. First, they clearly
underscore the commitment of the administration as well as the Congress to
environmental policy initiatives. Second, they give CEQ powers otherwise
held by few if any agencies in the executive office, except Office Manage-
ment and Budget, to guide and influence the policies and actions of other
agencies. Thus, whatever may be said of the actions of CEQ, they have
been carried out with a clear mandate from both Congress and the President
to harmonize Federal actions with environmental quality goals.
Section 102(2)(C) of the Act requires that any Federal agency proposing
legislation or planning to undertake an action "significantly affecting
the quality of the human environment" file an impact statement with the
Council. The statements describe the legislation or action, its impact,
and the alternatives considered. This draft statement must be circulated
by the initiating Agency to the public and to appropriate Federal, State,
and local environmental agencies. Comments received on the draft statement
become a part of the public record along with the final statement, which
should reflect the comments.
The draft environmental impact statement must discuss the following topics:
1. A description of the proposed action including information and
technical data adequate to permit a careful assessment of en-
vironmental impact by the commenting agencies.
2. The probable impact of the proposed action on the environment,
including impact on ecological systems such as wildlife, fish,
and marine life. Both primary and secondary significant conse-
quences should be included in the analysis.
3. Any probable adverse effects which cannot be avoided.
4. Alternatives to the proposed actions. A rigorous exploration
and objective evaluation of alternatives that might avoid some
or all of the adverse effects is essential. Sufficient,analysis
of such alternatives and their costs and impact should be covered
in order not to foreclose options which might have less detri-
' mental effects. ,-,..'.• : ; ;
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5. Relationship between local short-term ,uses ,of.man's environment
and the maintenance and enhancement of long-term .productivity.
6. Any irreversible and irretrievable commitments of resources
which would be involved in the proposed action should it be
implemented. ... . . .. ''"
The Council on Environmental Quality has issued guidelines on how agencies
are to meet this requirement (Federal Register 36, .7724 (April 23, 1971),
and most agencies have set up procedures, applying^the'requirement to their
own programs. The EPA procedure will be published in the Federal Register
within the next few weeks. The Food and ..Drug Administration published a
notice of their proposed impact statement procedures on July 12, 1972.
State governments prepare statements only when,their actions are supported
by Federal contracts, grants, or permits and the Federal agencies have
delegated the preparation authority to the State level. An example is
the Federal Highway Administration, which provides'matching grants for
many State highway construction programs. The draft ..statements are gener-
ally prepared by the State Highway Department; the Department of Transporta-
tion takes responsibility for the final statements.
Must industry prepare impact statements? Generally speaking, no. The
exception comes when an industry, action requires a.Federal license or
permit—such as a Corps of Engineers dredging permit or a transmission
:right-of-way across Federal land. When a regulatory permit or action
calls for a statement, the Agency will prepare the statement but may
require the private industry involved to file a preliminary environmental
report analyzing the impact of what it proposes to do.
The. draft statements must be made early enough in the Agency review/process
before an action is taken in order to permit meaningful consideration of
the environmental issues involved. In addition, the 90-day waiting period
requirement means that the Agency must anticipate a minimum 90-day wait
.from filing the draft statement to beginning action. To the. maximum extent
;possible no action is to be taken within 90 days after the draft, statement
has been: made available, nor. is it to be taken within 3.0 days of the final
statements availability. These waiting periods only apply to actions the
Agency can. take itself and may be modified with CEQ's consent when emer-
gency circumstances, expense to the government or impaired program effec-
tiveness make modification appropriate.
The CEQ guideline listed earlier contains an appendix which lists Federal
agencies with expertise in particular aspects of the environment which
should be asked to comment. In.the case of pesticides, the following are
listed:.
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Department of Agriculture
Agricultural Research Service
Consumer and Marketing Service
Forest Service
Department of Commerce
National Marine Fisheries Service
National Oceanic and Atmospheric Administration
Environmental Protection Agency
Office of Pesticides Programs
Department of the Interior
Bureau of Reclamation
Bureau of Sport Fisheries and Wildlife
Bureau of Land Management
Department of Health, Education, and Welfare;
In addition, State or local reviews may be relevant. Any individual or
organization may also comment on the draft statement: he may express sup-
port or opposition, suggest alternatives or point out project effects that
may have escaped the attention of its sponsors. These comments may be in
the form of a letter, a critique, or even a "counter-statement" setting
forth their views and analysis in as great a depth as the original itself.
The Agency preparing the statement is responsible for making it available
to all. All draft and final statements are listed in the CEQ publication
--102 Monitor, the National Technical Information Service, and the Environ-
mental Law Reporter. Additionally, the CEQ publishes regularly lists of
statements in the Federal Register. Copies can usually be acquired from
the Regional offices of the Agencies. Many who feel that they want to
comment on most statements from a particular Agency have their name on
the regular mailing list for commentators.
As the Agency supervising the whole progress, the Council on Environmental
Quality must pay special attention to maintaining the rules for the flow
of reports, leaving most substantive comments to the particular expert
Agency reviewers. The limits of CEQ's powers must also be noted. It has
no authority to veto the actions of any other Agency, nor even to require
an Agency to file the draft statement. It does have the power to review
Agency's actions and the responses of interested groups and to give ad-
vice to both the Agency and to the President. But in an intractable con-
flict with another Agency, CEQ's power is limited to its ability to persuade
the President to take action* Its influence can be explained only by its
success in persuading the President to adopt its recommendations or by its
success in persuading agencies to adopt its recommendations voluntarily
and thereby avoid later consequences in the wider forum of congressional,
judicial and public opinion.
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Federal Agencies have taken, modified, and avoided actions on the basis
of the NEPA environmental analysis. For example, the Department of De-
fense amended plans for munitions disposal. The Forest Service switched
from clear cutting to selective cutting in several National Forests. The
Corps of Engineers refused to grant some dredge and fill permits in order
to protect ecological and esthetic values.
With these introductory and explanatory remarks about impact statements
completed, the remainder of the discussion should cover their effect on
pesticide programs of the various Federal Agencies.
The Environmental Protection Agency has been involved almost continually
since its beginning on December 2, 1970, in reviewing impact statements on
pesticide programs. The first studied was' the USDA program for the control
of the imported fire ant with Mi rex and the correspondence came out at
about the same time (March, 1971) as our first policy statements on DDT,
aldrin and dieldrin, 2,4,5-T, and other controversial pesticides. The
second one of importance was the USDA gypsy moth control program. Our
responses were highly critical of the conclusions on environmental im-
pact derived from the information given in the statement. However, it
was not published until months after the actual spraying so it just drew
praise from the environmental organizations and served as an indicator of
the position the Agency might adopt for future programs.
The EPA Regions did review several Corps of Engineer programs for the clear-
ance of aquatic vegetation from navigable waters by the use of herbicides,
usually 2,4-D. However, they drew little notice.
In November 1971, the Office of Pesticides Programs was designated the
principal reviewer for all impact statements involving pesticides. A sys-
tem was devised so that the EPA's comments would reflect the total environ-
mental responsibilities of the Agency. The comments should strive to stimu-
late appropriate consideration of primary and secondary environmental ef-
fects by other Federal Agencies in their decision-making process. Comments
should stress fundamental of fact or policy and should be of a constructive
nature, suggesting, where possible, not only what should be improved, but
also how.
EPA comments are organized into one of the following categories:
Category 1. General Agreement Lack of ''bjections. The Agency has
no objections to the proposed action as described, suggests only
minor changes, or has no comments.
Category 2. Inadequate Information. The Agency feels that the state-
ment does not contain information to assess fully the impact of the
proposed project. The Agency's comments will request more information
about the potential hazards addressed in the statement, or ask that a
potential hazard not addressed be included.
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Category 3. Inadequate Information/Objection Raised. The Agency
feels that the statement does not contain- adequate information to
assess fully the environmental impact. However, from the informa-
tion submitted, we are able to ascertain that revisions will have
to be made.
Category 4. Major Changes Necessary. The Agency believes the pro-
posed action needs major revisions to adequately protect the environ-
ment.
Category 5. Unsatisfactory. The Agency believes the action is un-
satisfactory because of its potentially harmful effect. Furthermore,
the safeguards which might be utilized may not afford protection from
the hazards arising from this action. The Agency recommends that al-
ternatives to the action be analyzed further (including the possibility
of no action at all).
The Office of Pesticides Programs has served as the principal reviewer on the
following environmental impact statements:
Federal State Cooperative 1972 Gypsy Moth Suppression Program.
Treatment of 300,000 acres in Alabama, Connecticut, Delaware, Maine,
Maryland, Massachusetts, New Hampshire, New Jersey, New York, North
Carolina, Vermont, Virginia, and Wisconsin with carbaryl. There
may be a temporary reduction of certain beneficial insects and
arthropods.
Soil Inhabiting Insects Program. Application of chlordane at 35
high-risk locations (airports, military installations) in 21 states
to prevent long-distance artificial spread of plant pests.
Cooperative Diapause Control Program for Boll WeeviIs in Texas and
Mexico. The statement describes present and future plans, for con-
trolling the spread of boll weevils in the Texas High Plains. It
recommends the use of the insecticide aldicarb, in order to reduce
the use of malathion. Aldicarb is highly toxic and will be applied
only to rows in the margins of selected fields near ideal overwinter-
ing quarters. Some studies have been done to determine aldibarb's
effect on insects, animals, etc.
Cooperative Federal-State (North Carolina and South Carolina)
Regulatory Program for Witchweed, involving the use of 2,4-D
and paraquat. The objective of this program is to retard the
spread of main areas infested by witchweed plants and to eradi-:
cate small infested areas isolated from the main areas.
U.S. Air Force. Disposition of Orange Herbicide (a defoliant)
by Commercial Incineration at Deer .Park^..Harris County, Texas.,
and Sauget, Illinois.The empty drums will be decontaminated,
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crushed, and buried in a landfill pit. This statement involves
the discharge of 44.68 million pounds of CC^ into the atmosphere,
and the liquid water-salt effluent from HC1 acid scrubbing action
will discharge 12.4 million pounds of NaCl into a public stream.
Imported Fire Ant Cooperative Federal-State Control and Regulatory
Program. Aerial application of Mi rex to 20 million acres in Alabama,
Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina,
South Carolina, and Texas.
Federal-State Cooperative Spruce Budworm Suppression Project, 1972,
Aroostook and Penobscot Counties, Maine.Chemical treatment of
500,000 acres of State and private commercial woodland with Zectran.
1972 Siskiyou National Forest Herbicide Program (Josephine, Curry,
and Coos Counties, Oregon)"The selected herbicides 2,4-D, 2,4,5-T,
or atrazine will be applied to 213 separate tracts totalling 11,858
acres during one of two application seasons. Reduction of vegetative
competition to increase survival of newly planted conifer seedlings
is the treatment object.
Federal-State Cooperative Grasshopper Control on Western Range!and.
Chemical treatment of 2.5 million acres of rangeland with malathion.
Proposed Animal Damage Control Act of 1972. Repeal of the Act of
March 2, 1931.Restrict the use of poisons for killing predatory
animals on Federal lands. Role of the Department of the Interior
in animal damage control will consist of research, extension, regu-
lation of animal damage control on Interior lands, and administer
a phase-out, 3-year grant-in-aid program to the States for predatory
animal control. The proposal is national in scope, but largely af-
fects range lands in the West.
Herbicide Control of Big Sage Brush with 2,4-D (Beaverhead National
Forest, Madison and Beaverhead Counties, Montana).Specific control
areas are being planned and designated on the ground by the Ranger
with the assistance of specialists in ecology, wildlife biology,
soil science, and range science. The chemical 2,4-D may have some
effect on animal organisms and nontarget plants.
Removal of Canada Plum to Control Green Peach Aphid in Aroostook
and Penobscot Counties, Maine. The overwintering host plant
(Canada Plum) of the green peach aphid will be removed by chemical
and mechanical methods from certain test areas. The trees will be
cut and the stumps painted with ammonium sulfamate. Trees left un-
cut will be sprayed with the insecticide demeton.
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Department of Justice and Indiana State Government treated 65 sq.
miles of farmland and 65 linear miles of ditch and shoulder road
with 2,4-D in Pulaski County for eradication of Marijuana.
Demonstration of Modular Internal Spray System for spruce budworm
control in Lolo National Forest, Montana. One of the project ob-
jectives was to test the suitability of using large cargo aircraft
as spray planes in forest environment.
1972 Suislaw National Forest Herbicide Use Program. The selected
herbicides -- 2,4-D, 2,4,5-T, amitrole, atrazine, picloram, and
dicamba would be applied to 11347 acres to control specific types
of vegetation.
We have also supplied comments to other Principal Reviewers in EPA on the
following environmental impact statements:
Water Bank Program, USDA. Under the Water Bank Program, incentive
payments will be made to landowners and operators for conserving
waters, preserving or improving migratory waterfowl habitat and
other wildlife resources.
Wheat, Feed Grain, and Cotton Set-Aside Program. The Agricultural
Act of 1970 instructs the Secretary of Agriculture to provide for
a set-aside of cropland if he determines that the total supply of
wheat, feed grains, or cotton will likely be excessive, taking
into account the need for an adequate carryover to maintain reason-
able and stable supplies and prices and to meet a national emer-
gency.
U.S. Army Engineers and Virginia Commission of Game and Inland
Fisheries. Walker Dam Impoundment Aquatic Plant Control, New
Kent County, Virginia. Initiate program to control infestation
of el odea with diquat and potassium endothal.
Control of Eurasian Watermilfoil in TVA Reservoirs. There are
two methods of controlling watermilfoil: Water level management
to dry the plant by dewatering or by otherwise disturbing its
habitat, and application by 2,4-D herbicide applied by boats.
National Center for Toxicological Research, Pine Bluff, Arkansas.
Development of existing facilities for use by the Center with
initial action to be conversion of 29,000 sq. ft. of space to
animal holding and research use.
Approval of polyvinyl chloride liquor bottles. The Internal
Revenue Service prepared a statement because of the ,solid waste
disposal effect on the environment.
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As you heard the great number of impact statements are generated in the
Forest Service of the U.S. Department of Agriculture. In fact, USDA spent
over 2 million dollars in the preparation of impact statements on pesti-
cide programs, flood-control projects, and other projects in fiscal year
1972. This, at times, agonizing'appraisal caused the U.S. Department of
Agriculture to amend the way it normally conducts business. The Modular
Internal Spray System tested in the Lolo National Forest in Montana was
originally scheduled in the Flathead Indian Reservation in western Montana
but was changed during the preparation of the impact statement. Again,
the Forest Service cancelled a proposed spray program with 2,4,5-T for
the control of mesquite in the Coronado National Forest, Arizona, after
filing copies of the 'draft impact statement with CEQ. In our response
to the Forest Service program for using six herbicides-- 2,4-D, 2,4,5-T,
amitrole, atrazine, picloram, and dicamba— for controlling vegetative
growth, we suggested that the program be limited to the use of 2,4-D,
2,4,5-T, and atrazine. The Forest Service concurred with our recommenda-
tions and modified their program accordingly.
Again in 1972, the press cast us as completely antagonistic to the gypsy
moth control programs of the U.S. Department of Agriculture. Our com-
ments led to a reduction of about 50,000 acres in the planned 195,000
acres and the development of a monitoring study oh the effect of car-
baryl on birds, fish, and wildlife. We feel that information from this
study will help in assessing environmental damage. Additionally, the
final impact statement covered the cost-benefit aspect of the spray pro-
gram and some solid figures on the effect of the pest on real estate
values, tourism, erosion control, and aesthetics were generated.
Our responses are not always interpreted in a way we expect. In all cases
we have been, and we will continue to be, impartial in our judgments—no
matter what readjustments are necessary and no matter whom our comments
affect. We were very complimentary in our responses to- a Forest Service
program for eradication of sagebrush with 2,4-D in Beaverhead National
Forest, Montana. However, the State of Montana Department of Fish and
Game was highly critical of the proposed program and also of our response.
An exchange of views with this State Agency has already started and we
hope that out of this conflict can come mutual benefits.
The EPA publishes periodically in the Federal Register a listing of draft
statements that have been reviewed and commented upon. The listing in-
cludes the Federal agency responsible for the statement, the title of the
statement, and the classification of the nature of EPA's comments. Copies
of these comments are available from the Office of Public Affairs, EPA,
Washington, D.C. 20460.
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Earlier, I mentioned that the Food and Drug Administration recently pub-
lished a notice of their proposed environmental impact statement pro-
cedures. They are asking that manufacturers seeking premarketing clear-
ance of human and animal drugs, food additives and color additives in-
clude impact analysis reports with their submissions. Then, FDA itself
would act upon the reports and prepare the impact statements for the
required marketing clearances. At the present time, EPA does not re-
quire such.a report be filed with a petition for the registration or
establishment of a tolerarrce for a pesticide compound.
There are signs of a back lash against the National Environmental Policy
Act. Some of the antagonism springs from the uncomfortable burden of
paperwork and the cost in manpower and dollars. However, the most im-
mediate source of anxiety is the enthusiasm with which Federal courts
have been interpreting the Act and delaying Federal programs, especially
the public works projects throughout the country. It is not surprising
then, that there are several bills in the Congress to exclude certain
Agencies from the preparation of impact statements but it appears that
this will not include the pesticide-oriented programs.
I feel that we in the Environmental Protection Agency and you in your
official capacities should continue and expand our efforts in studying
these proposals which affect us and this world we live on. Thank you!
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USDA-APHS ENVIRONMENTAL STATEMENT
This statement was distributed by Mr. William Hoffman and
students reported on their work group findings in the course.
Title of Statement; Rangeland Grasshopper Cooperative Control Program
Type of Statement; Draft (X) Final ( )
Date; February 9, 1972
Type of Action; Administrative (X) Legislative ( )
Statement;
1. Description and Background
Grasshoppers are a serious pest in the Great Plains and Mountain States.
They can cause complete devastation to range and cropland during out-
breaks. No year passes without significant damage occurring to rangeland
in some areas. The pests compete with cattle and wildlife for grass and
browse, and during severe outbreaks, feeding areas may be completely
devastated. Cattle are sometimes sold early or shipped to other range
areas because of grass depletion. These outbreaks can surpass the abil-
ity of individuals to handle the problem on a local or community basis.
Because of this, it has been determined that federal assistance in
protecting range grass and preventing severe population buildups which
may lead to large-scale migrations to agricultural crops is justified and
in the public interest.
Most range grasshoppers are not general feeders as are crop grasshoppers.
Some of these species eat only grass, some feed on plants other than
grass, and some prefer shrubs. Since as many as 20 species may be found
living together, nearly all range vegetation is subject to attack despite
the specialized feeding.
Even when the infestation of a range is light, with an average of six or
seven grasshoppers to the square yard, the grasshopper population on each
10 acres consumes grass at about the same rate as a cow. If the grass is
sparse, the amount thus destroyed may reduce the supply to the point
where cattle can no longer subsist on it. During outbreaks, when there
may be 30 to 60 grasshoppers to the square yard, all the grass may be
destroyed.
The amount of economic damage caused by a given number of grasshoppers on
a given area of range varies with changes in temperature and rainfall.
During cool weather and abundant rainfall, grass is likely to be plenti-
ful, and the amount consumed by the grasshoppers is not economically
significant. In hot dry weather, however, grass is likely to be scarce,
and the amount consumed is a serious matter. Also, some grasshoppers eat
more in hot weather than in cool weather (9).
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During the midthirties, grasshoppers were so prevalent in the Midwest
that farmers and ranchers could not cope with the situation. Funds were
first appropriated by the Congress in 1934 to cooperate with the States
in organized grasshopper control programs. Since 1937, a program has
been conducted almost annually with funds provided partly by individuals,
counties, states, and the federal government in accordance with the needs
as determined by an annual grasshopper survey.
In 1948, it was recommended by State officials from the States affected
by the grasshopper problem that, in view of the effective insecticides
available, the federal government should be relieved of the burden of
assisting farmers in combatting cropland grasshoppers. It was reasoned
that the cropland farmers were now able to protect their crops and crop
protection as such was no longer considered a federal responsibility.
Where grasshoppers originate on a particular farm, doing damage only on
that farm, individual action is sufficient. However, if they are present
in such numbers that movement from one farm to another could occur, com-
munity action is needed. When severe outbreaks extend over large areas,
the cooperation of county, State, and federal agencies is essential to
successful control. This is particularly true in range areas where some
land is privately owned, some State owned, and some owned by the federal
government. Only a few species attack crops, but more than 100 species
feed on range vegetation. If not controlled through an organized effort,
many of these will move into cropland from denuded range areas. This new
policy was implemented in 1949 with the federal government furnishing
only technical assistance for grasshopper control in croplands.
The objective of the present program is to control threatening economic
populations in cooperation with ranchers, State, and federal agencies to
protect rangeland and prevent population buildups which could spread to
valuable croplands. The treatment of incipient outbreaks reduces the
extensive use of pesticides should the pest be permitted to spread into
other range areas or into cropland.
In 1951, the present policy was established whereby the cost of rangeland
grasshopper control would be shared by individuals, States, counties, and
the federal government, with the latter providing one-third of the total
cost on private and State lands. Survey and control on federal lands
such as those administered by the Bureau of Land Management and the Bureau
of Indian Affairs, U.S. Department of the Interior; and the Forest Ser-
vice, U.S. Department of Agriculture, continued to be the responsibility
of the federal government. To support this effort, memoranda of under-
standing have been consummated between Agricultural Research Service and
the Forest Service and between USDA and the USDI. Since 1951, when modern
insecticides came into general use in the grasshopper program, there have
been no widespread outbreaks or severe losses. With the exception of 4
years, in the late fifties and the years 1966 and 1967, the use of control
materials has been greatly reduced. This has been due to the development
and use of improved methods and procedures which resulted in more effec-
tive control.
Grasshoppers have been at an unusually low level for the past several
years. However, during 1971, heavy population buildups occurred in sev-
eral western States. In any given year, all acreage that should be
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treated does not receive treatment. Landowners as a rule do not favor
treatment in years of light infestations, nor do they favor treatment
unless damage is visible. When damage is occurring, it is generally too
late to .organize and prepare for a cooperative program. Too often, the
rancher that was aware of the potential in March and April and not inter-
ested in a program is desirous to participate in mid-July or early August
when the grasshoppers are in the adult stage and egg laying is taking
place. Treatment at that time does not reduce future populations that
could build up under weather conditions favorable to grasshopper develop-
ment. In an ideal control program where grasshoppers are reduced to one
or less per square yard, they will probably remain harmless for several
years. The same area under these conditions is seldom treated more than
once in 5 to 10 years.
Despite large-scale control programs in 1971, severe damage to crops in
Idaho was caused by grasshopper migrations from range areas. Damage to
the range grasses also occurred in Idaho, as well as in Colorado, New
Mexico, Oregon, and Wyoming. If conditions are favorable for grasshopper
development in the spring of 1972, serious outbreaks can be expected.
If control programs are required in the infested States, the insecticide
malathion will be applied by contract aircraft at the ultralow volume
(ULV) rate of 8 fluid ounces or 0.64 pound of active ingredient per acre.
The insecticide carbaryl has also been used in recent years for grass-
hopper control with good success. When carbaryl is the insecticide of
choice, it is applied at the rate of 16 fluid ounces of 8 ounces active
ingredient per acr.e. The choice of approved chemicals is normally
mutually agreed upon by the cooperators. One application of malathion
or carbaryl is required for control. It is sometimes necessary to
retreat an area and apply a second application when rains occur immedi-
ately after treatment. Approximately 2 million acres of rangeland in
the western States may require treatment in 1972. The size of the areas
may range from 5,000 to 400,000 or more acres. Some of the work will be
done on State land and the public domain, but primarily on privately
owned land.
In 1971, the actual cost of treating with malathion, including applica-
tion, was about $0.60 per acre. The one-third cost to the rancher was
about $0.20. However, where cropland is interspersed in with the range-
land, the grower pays the entire $0.60 per acre for the cropland treat-
ment. Due to rising costs, the per acre cost in 1972 may be slightly
higher.
Adult grasshopper surveys are conducted during the late summer and fall
each year, and a map is prepared showing the areas and potential severity
of infestations for the following year. The surveys are made by trained
personnel making a number of stops in each county. The number and loca-
tion of these stops are dependent on the nature of the infestation, the
size of the county, and the supervisor's knowledge of grasshopper devel-
opment during spring and'summer in his area. The adult survey maps are
furnished to other federal agencies, to county agents for dispersal to
farmers and ranchers, and to other interested groups. State-federal
meetings are held with the ranchers during the fall and winter months,
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apprising them of infestations and expected need for control the coming
year. After grasshoppers begin hatching in the spring, nymphal surveys
are made where economic populations were found during the adult surveys.
This survey is the criterion for determining whether or not control will
be necessary. Before any control is undertaken on private land, the
ranchers must show an interest and cooperate in the program.
Research studies have shown that on the average, eight or more grasshop-
per nymphs per square yard in the fourth and fifth instar can cause
economic damage. For most species, there are five instars or stages of
development preceding the adult stage. This can vary with the season.
In some cases, when grass is sparse, fewer grasshoppers can cause damage;
and when grass growth is lush, the range can sustain higher populations
without significant loss.
Statutory Basis for Conduct of Program
The Secretary of Agriculture is authorized either independently or in
cooperation with authorities of the States concerned, organizations, or
individuals, to carry out such methods as may be necessary to eradicate,
suppress, control, or retard the spread of certain insect pests, plant
diseases, and nematodes, under enabling statutory authorities granted the
U.S. Department of Agriculture by the Contress. The authorities pertain-
ing to the control of grasshoppers are listed below:
Incipient or Emergency Control of Pests
(Joint Resolution of April 6, 1937, as amended;
Title 7, United States Code, Sections 148-148e.)
Organic Act of the Department of Agriculture
(Act of September 21, 1944, as amended;
Title 7, United States Code, Section 147a.)
Cooperation with State Agencies in Administration
and Enforcement of Certain Federal Laws (Act of
. September 28, 1962; Title 7, United States Code,
Section 450.)
Each State has basic pest control authority permitting participation in
cooperative pest control programs.
2. Environmental Impact
Malathion treatments for grasshopper control have been monitored for
several years. Results of these studies show that, while some beneficial
insects and other nontarget organisms are affected, any damage that may
occur is of limited extent and duration. In monitoring studies on fish
and wildlife in Nebraska, Utah, and Wyoming on grasshopper control, it
was found that technical grade malathion sprayed at the rate of 8 fluid
ounces or 0.64 pound active ingredient per acre appeared safe for ter-
restrial and aquatic wildlife when adequate precautions are taken in
sensitive areas.
Malathion was applied by aircraft to approximately 49,000 acres of
scattered grassy parks throughout the Big Horn National Forest of Wypming
in August of 1965 (2). The rate was 8 fluid ounces, ULV, per acre.
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Observations of relatively small trout streams containing brook and
rainbow trout were made. The treatment did not affect the trout, although
brain cholinesterase levels were lowered. The malathion treatment had a
fairly severe effect on fish food organisms, although some types of
organisms apparently remained unaffected. Similar studies were conducted
in July and August, 1966. These were conducted to obtain additional
information on the effects of ULV malathion on fish and fish food organ-
isms. Fairly large streams contained good trout populations. On the
Wind River Indian Reservation of Wyoming in August 1966 (3), the study
indicated slight effects 'on fish and other aquatic life. Bottom animal
samples indicated some reduction in fish food organisms, but numbers were
adequate for repopulation. Whenever possible, stream coverage was made
transverse to the stream flow to minimize effects on aquatic life. How-
ever, in fast-flowing streams where the line of flight was parallel to
stream flow, the effects on aquatic life were not observed to be any more
significant than when the line of flight was flown across the stream. No
fish mortality was observed, either in unconfined wild fish or in hatchery
fish confined to live boxes in the Wyoming tests.
On the Dixie National Forest study in Utah, July 1966 (4), the most
noticeable effect of the spray application on aquatic life was the mor-
tality of about eighty 3- to 14-inch brook trout. Most of the mortality
was confined to areas where definite overlapping of the swath patterns
was observed. The spray patterns were made mostly parallel to the east
fork of the Sevier River, a very slow-moving, meandering meadow stream
with many wide, shallow polls. Brain cholinesterase levels in samples of
these dead fish were near zero. All mortality occurred in unconfined
wild fish, with no mortality of fish confined in live boxes in the same
area. Apparently, wild unconfined fish obtained additional chemical by
feeding on dead insects. Observations, however, indicated a fairly good
fish population remaining in most areas after the spray application.
While no specific studies were conducted, crew members reported they
observed no adverse effects or behavioral changes in any forms of wildlife.
Similar results to the Wyoming tests were obtained from a study on the
Crow Indian Reservation in Montana in July of 1966 (7). Malathion was
applied at 8 fluid ounces of ULV or 0.64 pound active ingredient per acre.
No dead fish were observed in the stream sampled or in live boxes. The
most striking effect of the treatment was the kill of aquatic organisms,
although quantitative bottom samples were not greatly different. The
monitoring study that was conducted in northwestern Nebraska in 1964 (13)
indicated that small mammals did not appear to be affected by the treat-
ment. Other studies, such as the cooperative study performed by Marston
(8) and Pruess and Raun (10,11,12) indicated no long-lasting detrimental
effects on nontarget arthropod fauna.
Ultralow volume malathion is toxic to bees when applied while plants are
in bloom and the flowers are visited by working bees (5, 6). Precautions
are taken by notifying beekeepers of malathion applications where range-
land treatments are made in close proximity to bee yards. This permits
moving the hives when possible and feasible during the most critical per-
iods. When the colonies cannot be moved, they are marked by a flag to
prevent spraying directly over them if possible. It also has been found
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that covering the hives with wet burlap at the proper time reduces' the
damage that may otherwise be done (6).
Guidelines are furnished to the federal supervisors for their use when
the cooperative State-federal-rancher control program is organized.
Safety to bees is discussed at all planned conferences with coqperators,
including the ranchers, and precautions will be included in the work
plans. Precautionary efforts are not always effective, however, in
handling this difficult problem. This is demonstrated by the fact that
several beekeepers filed claims for bee losses under the Agricultural
Act of 1970, Public Law 91-524, Statute 1382, November 30, 1970.
The grasshopper programs are under the direction of trained federal per-
sonnel, including skilled pilots, experienced in the applicatipn and use
of pesticides. The contract pilots will be experienced, and in most
western States, a State applicator's license is required. However, all
pilots and aircraft meet Federal Aviation Agency requirements and are
checked by USDA pilots before the work is started. Boundaries of treat-
ment areas are easily identifiable from the air. Special precautions
will be taken when spraying over water and other sensitive areas.
3. Favorable Environmental Effects
The objective of this program is to control threatening economic popula-
tions in cooperation with ranchers, State, and federal agencies to pro-
tect rangeland and prevent population buildups which could spread to
valuable croplands. The treatment of incipient outbreaks reduces the
extensive use of pesticides should the pest be permitted to spread into
other range areas or into cropland. Over the years, much research has
been done on this pest, not on just a single species, but on a number of
different species native to the western United States where most damage
has occurred. The research has included biology of the pest, life history
and habits, including flight movements, damage done to various crops by
different species, and continued studies on control. It has been found
by research that if incipient outbreaks of certain species are left to
go unchecked, severe outbreaks can occur. This has been borne out by the
history of the development of severe infestations.
The program as it has been designed and conducted since 1951 has been
successful in preventing widespread catastrophic outbreaks which formerly
occurred. With the exception of 2 years, 1957 and 1958, the use of con-
trol materials has declined. This has been due to intensive survey
procedures in finding incipient infestations early and treating them
before they build up to unmanageable proportions, plus the fact that we
have effective control materials and efficient methods of application.
The grasshopper inflicts damage beyond yield losses to rangeland vegeta-
tion.
Losses under Present Program
! '
Under this program, annual losses to grasshoppers in the western and
western States are as follows:
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Millions of Millions of
Crops Dollars Rangeland Dollars
Yield losses $18.919 Yield losses $4.397
Control cost .017 Control cost .081
$18.936 $4.478
GRAND TOTAL: $23.414
Crop losses from bordering range areas were estimated from information
furnished by survey entomologists. These estimated losses of nine crops
were then extended to the 18 western States that routinely have native
grasshopper populations. Control costs on these crops were estimated to
include insecticide treatments to an average of 200,000 acres annually
at a cost of $0.85 per acre. Rangeland yield losses were estimated from
known consumption of rangeland vegetation by grasshoppers. This consump
tion of herbage and browse was converted to dollars using the average
values of $3.50 per acre with an average per acre production of 0.688
tons of herbage and browse, which were obtained from U.S. Forest Service
and represent weighted average values for the 228.9 million acreage of
Great Plains ecosystem found throughout the western United States. Con-
trol costs on rangeland in the western States were obtained from program
records and represent the actual cost of the grasshopper program to the
ranchers .
Losses with No Program
Without the program, the estimated annual losses to grasshoppers are as
follows :
Millions of Millions of
Crops Dollars Rangeland Dollars
Yield losses $ 99.563 Yield losses $17.962
Control cost .594 Rehabilitation
°f ran8eland 5'475
$100.157
Control cost .830
$24.267
GRAND TOTAL: $124.424
Without a cooperative grasshopper program, populations on the public land
would not be controlled. Presently, 23 percent of infested rangeland is
on the public domain. Those populations on public land would overflow
and move onto range and cropland. The lack of subsidy (in form of cost
sharing on a one-third basis, rancher, State, and federal) would dis-
courage the ranchers from treating rangeland until or unless populations
were obviously threatening. Thus, without the cooperative program,
grasshopper populations would be more dense and would infest a greater
number of acres. These populations also would overflow and damage crop-
land. The estimated losses without the cooperative program were based on
available information and represent the best knowledge available. Assum-
ing that the residual life of the cooperative program is 14 years and
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that the program is discontinued next year, the accumulated discounted
(10 percent interest) benefits and costs of the cooperative grasshopper
program are estimated at $600.752/$12.442 million for a benefit cost
ratio of 48:1.
This program, by the strategic use of insecticides on rangeland, is
eliminating the need by the rancher and farmer to employ greater quanti-
ties of insecticides to protect his rangeland and cropland. The acreage
treated under this program averaged 0.649 million annually for the past
10 years. Without a cooperative program, the rangeland acreage that
would be treated by the rancher is estimated at about one million acres
annually. Cropland acreage treated for grasshoppers would rise from
200,000 to 675,000 annually. In terms of insecticide consumption, the
benefit of the cooperative grasshopper program is estimated at 6.29 mil-?
lion pounds of malathion annually, In addition, it is estimated that an
average of 300,000 acres of rangeland would be denuded annually by grass-
hoppers. The impact of this effect on the environment, which this pro-
gram is preventing, has not been estimated.
4. Adverse Environmental Effects Which Cannot be Avoided
The adverse environmental effects which cannot be avoided consist of the
impact of the insecticide malathion on the ecosystem when used to achieve
the program objective. The selective acreage where malathion^ will be
sprayed and the low rate of application poses no known adverse long-term
effect on the environment. Malathion at the rate used for grasshopper
control has a residual toxicity in the field of not more than 7 days.
5. Alternative to the Proposed Action
Grasshoppers may be controlled by these principal means: 1) Natural ene-
mies, 2) cultural, and 3) chemical. Natural enemies are present whenever
grasshoppers are found. However, during grasshopper outbreaks, the
buildup of natural enemies lags behind grasshopper population buildups
and seldom becomes a significant factor in sufficiently preventing eco*-
nomic losses. Research has been unsuccessful in harnessing biological
agents for control of grasshoppers. Cultural controls provide a valuable
supplement to chemical control in cropland areas for certain species of
grasshoppers. However, cultural control is unsound economically and
ecologically for control of rangeland grasshoppers.
Chemical control is judged to be the only presently available method for
economically controlling grasshoppers to achieve this program's objective.
During the early days of this program, insecticides were used extensively
in baits. In the early 1950s, aerial application of modern insecticides
significantly increased man's ability to control grasshoppers, covering
larger areas more quickly with less material at a lower cost. The use of
these modern insecticides has permitted reducing the average population
density of grasshoppers throughout the western States to the extent that
outbreaks, which were common before 1950, have not occurred since. Crop
losses from grasshoppers are now nearly insignificant (estimated at 0.57
percent of the farm value of host crops). The program originated from
farmers seeking relief from crop damage by grasshoppers.
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6. Relationship between Local Short-Term Uses of Man's Environment
The short-term objective of this program is to control rangeland grass-^
hoppers. The long-range objective is to protect crops from rangeland
grasshoppers. Sacrifices on the short-term objective will lead to an
increase in losses outlined previously in this statement for "no program."
In essence, there exists a balance between man's use of the land in the
western States for the production of food and fiber and the use of this
same land by other elements of the ecosystem. Grasshoppers are a major
competitor of man for the use of this land. The cooperative grasshopper
control program is believed to be the most effective method of swinging
this balance in favor of man.
The present cooperative grasshopper control program reflects the public's
commitment to use the resources of the western States for the production
of food and fiber for mankind.
7. Irreversible of Irretrievable Commitments of Resources
The effect of malathion as used in this program in the western States is
temporary and transient. It is believed that, without a cooperative
grasshopper program, the balance between man and grasshoppers that exist-
ed prior to this program would be reestablished in about 10 years.
8. Consultation and Review with Federal, State, and Local Agencies
The rangeland grasshopper control program on private lands is a coopera-
tive undertaking jointly planned and financed with the States and ranchers
in the infested areas. State and rancher meetings are held during the
winter and early spring months to determine the need for a control pro-
gram. The need is based on the adult surveys made in the fall and veri-
fied with nymphal surveys made after the hatch begins in the spring.
Often bad weather at the time of hatch can influence the populations to
the point where control will not be required. Memoranda of understanding
are in effect in every State where control may be required. These are
supplemented by a detailed work plan for each program in a State and are
approved and agreed to by the cooperators.
This program has been reviewed each year and approved by the Federal
Working Group on Pest Management responsible to the Council on Environ-
mental Quality. Personnel of the Plant Protection and Quarantine Programs
of the Animal and Plant Health Service contact responsible federal and
State representatives of conservation and research agencies such as the
Fish and Wildlife Service to notify them of any anticipated control
program and encourage monitoring activities where applicable.
Control programs on federal lands are the responsibility of the Plant
Protection and Quarantine Programs, APRS. Memoranda of understanding
have been consummated with the Forest Service and the Department of the
Interior. These memoranda of understanding provide that appropriate
supervisors in the cooperating agencies will be furnished information on
the following:
209
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1. Recommendation of control needs*
2. Insecticide or insecticides recommended for control opera-
tions.
3. Assessment of the proposed and alternate insecticide formu-
lation and application practices upon:
a. Wildlife, both game and nongame species.
b. Contamination of forage, water, and other resources.
c. Comparative costs.
4. Damage potential to forest of conservation land systems and
nearby lands if no control action is taken.
As circumstances warrant, Plant Protection supervisors meet with repre-
sentatives of the other federal agencies and private landowners with an
interest in grasshopper control.
A working copy of this statement was circulated for review within the
Department. Comments and suggestions received were considered and where
applicable, have been incorporated into the draft. Any problems, pbjec^
tions, or suggestions received from other federal, State, and local
agencies and from private organizations and individuals will be discussed
in the final statement.
References Cited
American Cyanimid Company. 1964. Malathion, a proven insecticide.
American Cyanimid Company Technical Bulletin*
Big Horn Grasshopper Control Project, Big Horn National Forest,
Wyoming. Jan. 13, 1966. Special report. Pesticide surveillance
program. U.S. Fish and Wildlife Serv., Bur. Sport Fish, and Wild-*-
life, Div, Fish. Serv., Ft. Collins, Colorado.
Henderson, C. March 21, 1967. Little Wind Grasshopper Control
Project, Wind River Indian Reservation, Wyoming. Special report.
Pesticide surveillance program. U.S. Fish and Wildlife Serv., Bur.
Sport Fish, and Wildlife, Div. Fish. Serv., Ft. Collins, Cplorado.
Henderson, C. Feb. 23, 1967. Podunk Grasshopper Cpntrol Project,
Dixie National Forest, Utah. Special report. Pesticide surveillance
program. U.S. Fish and Wildlife Serv., Bur. Sport Fish, and Wildr-
life, Div. Fish. Serv., Ft. Collins, Cplorado.
Johansen, C. A. and coauthors. 1965. Bee poisoning hazard of undi-
luted malathion applied to alfalfa in bloom. Wash. Agr. Expt. Sta.
Cir. 455.
Levin, M. D., W. R. Forsyth, G. L. Fairbrother, and F. ?. Skinner,
1968. Impact on colonies of honey bees of ultrar-low volume (undilut^
ed) malathion applied fpr control of grasshoppers. 4. Eqon. Ent, 61
(l):58-62.
210
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7. Malathion Grasshopper Control Project on the Crow Indian Reservation
in Yellowstone and Big Horn Counties, Montana. May 1967. U.S. Fish
and Wildlife Serv., Bur. Sport Fish, and Wildlife, Div. Fish. Serv.,
Portland, Oregon.
8. Marston, N. Feb. 22, 1967. Monitoring the effects of ULV malathion
spray programs for grasshoppers on nontarget arthropods in Wyoming,
1965-67. Terminal report. Dept. Entomology, Univ. Wyoming, Laramie.
9. Parker, J. R. and R. V. Connin. 1964. Grasshoppers, their habits
and damage., USDA Information Bulletin No. 287.
10. Pruess, K. P. and E. S. Raum. 1968. Project WASP (Wide Area Spray
Program), annual report. Dept. Entomology, Univ. Nebraska.
11. Pruess, K. P. and E. S. Raum. 1969. Project WASP (Wide Area Spray
Program), annual report. Dept. Entomology, Univ. Nebraska.
12. Pruess, K. P. and E. S. Raum. 1970. Project WASP (Wide Area Spray
Program), annual report. Dept. Entomology, Univ. Nebraska.
13. Robertson, K., B. Schoenecker, and L. C. McEwen. Feb. 11, 1965.
The effects of the 1964 grasshopper control program in Sioux County,
Nebraska. U.S. Wildlife Service, Nebraska Dept. Agriculture and
U.S. Plant Pest Control Division.
211
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212
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POLYCHLORINATED BIPHENYLS: AN INDUSTRIAL POLLUTANT
Richard E. Johns en
The polychlorinated biphenyls- (PCBs) are a relatively new class
of environmental pollutant of worldwide'-distribution causing wide-
spread, concern to pesticide chemists, ecologists, and, more recently,
to governmental agencies both here in the United States and abroad.
In the U.S., they are produced solely by the Monsanto Chemical Co.
and marketed under the trade name Aroclor. The PCBs are also manu-
factured in Japan under the trade name Kanechlor, in Germany under
the name Clophen, in France under the name Phenoclor and in the
U.S.S.R. Monsanto has released production figures from 1960 through
half of 1971 indicating a total production of 353,000 tons (1). Of
this amount, about 42,000 tons were exported. Since the PCBs have
been in widespread use since 1930, total production just in the U.S.
must be staggering. Worldwide, production has been conservatively
estimated at about 100,000,000 Ibs. annually. Monsanto markets PCBs
as products ranging from 21 to 68 percent chlorine by weight. For
example, Aroclor 1254 represents a polychlorinated biphenyl formu-
lation containing 54 percent chlorine by weight. The first two
digits represent biphenyl. Figure 1 shows the chemical similarity
of decachlorobiphenyl, the most highly chlorinated biphenyl, to
another controversial compound, p,p'-DDT.
Since PCBs are manufactured by the direct chlorination of bi-
phenyl molecules, there are theoretically about 210 compounds and
isomers possible. Of this number about 102 are probably depending
on the degree of chlorination and the positions of the chlorine
atoms on the rings. This fact considerably complicates the pic-
ture since we are not dealing with a single chemical compound.
The fact that the polychlorinated biphenyls have not been
found in the environment until recently is. somewhat of a mystery.
However, in contrast to DDT, they never were deliberately distrib-
uted into the environment and thus no one was really looking for
them in environmental media. Secondly, analytical instrumenta-
tion to positively identify them were not readily available until
the past few years.
Figure 1
Chemical structure of p,p'-DDT and decachlorobiphenyl
ci I ci
Cl
p,p'-DDT Decachlorobiphenyl
213
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These chemicals were first discovered as environmental con-
taminants in Sweden in 1966 (2) and in the U.S. the following year.
It is interesting to note the more than 35 year interval between
their initial industrial use and their first reported environmental
occurrence.
Why are they now widespread in the environment? Table 1
sents a brief summary of the environmental occurrence of PCBs.
This table needs constant revision as the literature on PCBs is
becoming very abundant.
England
Japan
Scotland
Netherlands
Antarctica
Panama
Baltic Sea
Sweden
United States
California
Colorado
Table 1
Environmental occurrence of PCBs
- Rain water
- River water
- Brown seals
- Mussels
- Adelie penguin eggs
Brown pelican eggs
- Cod
<- Fish and marine birds
- Human hair and adipose tissue, bald eagles,
sewerage
- Peregrine falcon, fish (anchovy, shiner
perch, tuna, English sole, Jack mackeral,
hake)
- Human milk, digested sewerage sludge, river
water
It is apparent that, for the most part, those areas e?cperi-
encing residues of PCBs are the more industrialized nations. How-
ever, once residues appear in rivers and oceans their distribu-t
tion can be widely broadened. Through 1969, there were apprpjci-r
mately 55 general uses of the PCBs. Table 2 presents a resume
of these uses (some uses are combined) to illustrate how broad
their industrial application base has become in or on various
commodities.
214
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Table 2
Uses of polychlorinated biphenyls
Flame proofing of cellulose fabrics
Electrical insulating fluids
High-vacuum systems •
Anodized aluminum surfaces
Plasticizers in plastics
Hydraulic fluids
Insultation products and insulating
liquids
Heat transfer exchange fluids
Lubricating compounds
Plastic laminating material and
adhesives
Corrosion inhibitors and coatings
Extreme high pressure lubricants
Antistatic coatings for plastics
Thermographic copy paper and
solutions
Rubber and dyes
Lacquer and polishes
Permanent stencils
Concrete coatings
Paints, waxes and varnish
coatings
Cutting oils
Metal decorating and printers
ink
Graph.te mixtures
Grease-mashing materials
Asphaltic materials
Putties and cellophane
Peneling materials
Flame retardant coatings
Fingernail polish
In fairness to Monsanto, they have voluntarily agreed to
limit the use of PCBs to sealed systems in response to mounting
evidence that PCBs have widespread distribution and are a poten-
tial hazard.
One might again ask the question of why they are widespread
in the environment? Table 3 lists some of the physical properties
of PCBs, properties which have insured their environmental persis-
tence.
Table 3
Physical properties of polychlorinated biphenyls
1. Low vapor pressure (high boiling point)
2. Low water solubility (high lipid solubility)
3. High dielectric constant (non-conducting)
4. High thermal stability (to 870°C.)
5. Permanently thermoplastic
6. High resistance to acids, alkalies, and other corrosive
chemicals
7. High resistance to oxidation and environmental breakdown
8. Vary from oily liquids to white crystals and hard transparent
resins.
Figure 2 lists the structure of DDT and two of its metabolites,
DDE and TDE. Note that metabolism is limited to the two-carbon
chain between the phenyl groups. The PCBs lack this "handle" for
215
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metabolism and, partially for this reason, are considerably more
resistant to breakdown than is DDT.
Figure 2
Structure of p,p'-DDT and its metabolites DDE and TDE
H ' H
// \Vci C.-U/ \\-r.Jf NVn ri-V. N>- C-
DDT
DDE
When gas-liquid chromatography (GLC) replaced traditional
chemical methods, such as colorimetry, in the early 1960*s in
the pesticide analytical, laboratory, it became apparent that
tissues of certain animals - particularly the fish eaters - con-?
tained "unknown" peaks in addition to the known pesticides.
Using GLC with detectors relatively specific for chlorine con-
taining compounds, it was known that they were chlorinated
chemicals. These unknowns had been the subject of much dis-
cussion and concern although little had been written about them.
On the GLC tracings, the PCBs, for example Aroclpr 1254,
have 14 or more peaks, some of which overlap those of the DDT
group and coincide with other insecticides as well. Figure 3
illustrates typical GLC chromatograms of Aroclpr 1254 in the
center, an extract of digested sewage sludge on the top and a
mixture of the two on the bottom. It is apparent that a chlori-r-
nated hydrocarbon mixture very similar, if pot identical to
Aroclor 1254 is present in the sewage sludge. One can readily
see from the complexity of the chromatrogram for a PCB how con-
fusion can and has resulted in both identifying residues and
quantifying residue data when both PCBs and DDT or other pesti-
cides are present in the same extract.
One might next ask the question of how do the PCBs get into
environmental media. Table 4 presents some of the possible
routes. Very little is currently known about this aspect of the
PCBs.
216
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- 3.0 UL - SBWGE SUDZ EXTRACT, 10 UG/UL L .1 —
1.0 UL - AR m 0.8 NB/UL ^
i ' ': 3.5 UL Mix - IP n. Afi 12» + 7.5 «.
EXTRACT
_ -I--
Figure 3. Electron-capture gas chromatographic analysis
of a digested sewage sludge extract, Aroclor 1254, and a
mixture of the two.
2 17
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Table 4
Possible routes of PCBs into the environment
1. Incineration of waste materials
2. Accidental leaks of equipment (e.g. heat transfer systems)
3. Weathering or friction-wearing of the many materials having
PCS's as an ingredient
4. Sewage disposal systems
5. Interaction with food products in their uses as an ingredient
in substances like plastics and paints.
My laboratory has been involved in a number of studies with
PCBs. One study involved measuring the volatilization of Aroclor
1254 and 1260. Even though their vapor pressures are very low,
about 5% was volatilized after one week from a deposit and slightly
more from an aqueous suspension, both under ambient laboratory
conditions. It was evident that the lower chlorinated compounds
volatilized more rapidly.
This laboratory has found, as indicated earlier, PCBs in di-r
gested sewage sludge from Fort Collins. We have also found PCBs
in sludge from a number of other locales in Colorado. However,
GLC evidence is not conclusive in identifying a compound.
More information was gained by examining both the extract
and Aroclor 1254 on a microcoulometric gas chromatograph, a GLC
with a detector specific for chlorine. This data also indicated
that the extract contained PCBs essentially identical to Aroclor
1254. To get structural proof that the unknown is indeed Aroclor
1254, infrared spectra were obtained as shown in Figure 4. The
infrared spectrum of the sewage sludge extract is consistent with
the known Aroclor 1254 spectrum. Note the aromatic substitution
absorption bands between 800 and 900 cm" and the consistent
"fingerprint" area of 1000-1200 cm'1.
The next aspect of the work was the separation and identifi-
cation of sewage sludge components by GLC coupled with a mass
spectrometer (AEI Model MS-12). A direct probe analysis was
made with both the extract and Aroclor 1254, using a concentrated
sludge extract whose physical appearance was similar to 1254,
being a clear and very viscous liquid. The results indicated
that the highest ispmer in both samples had a mass of 392 indi-
cating a heptachlorobiphenyl. The spectra obtained showed the
intense fragment ions produced by the consecutive loss of chlo-
rine atoms from the parent ion.
The data from the GLC coupled to the mass spectrqmeter gave
proof that the sewage sludge extract contained 4 tetrachloro-,
3 pentachloro-, 4 hexachloro- and 2 heptachlorobiphenyl isomers.
The peaks from the sludge extract were identical in mass to
those of Aroclor 1254 confirming the presence of PCBs in the
sludge.
218
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'.5 H-0
9.0 10.0
MICRONS
15.0
20.0
1300 1200 1100 1000
600 500
FREQUENCY I CM 'i
Figure 4. Infra-red spectra of Aroclor 1254 (A) and
a digested sewage sludge extract (B).
219
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We also have additional supporting GLC data using a Coulson
electrolytic conductivity detector, thin-layer chromatographic
data and spectrophosphorimetric data.
Recent work, on the metabolism of Aroclor 1254 and a number
of known PCB isomers, in soil indicates no breakdown in a system
where DDT is almost 100% metabolized. A:recent study showed that
PCBs are readily absorbed into the root systems of certain plants.
We have also confirmed the presence of PCBs in water and sediment
downstream but not upstream frorr. a local sewage plant outfall.
There are a number of research needs that should be investi-
gated to clarify the many questions remaining. Such needs are to
determine the source of pollution, the extent of biological con-
centration, toxicity studies, transport mechanisms and metabolism
in various biota and ecosystems.
Literature Cited
1. Anonymous. 1971. Toxic substances; Monsanto releases PCB
data. Chem. Eng. News, p. 15 Dec. 6.
2. Anonymous. 1966. New Sci. 32:612.
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EPIDEMIOLOGY OF ANIMAL POISONINGS OTHER THAN HEAVY METAL POISONINGS
Frederick W. Oehme
Epidemiology is defined as the science of the prevalence of a disease or
diseases in a community. In human medicine this refers essentially to conta-
gious or infectious diseases and their spread throughout a population. In
veterinary medicine, infectious diseases are only a portion of the disease
problem. Disorders produced by chemicals (poisonings) and improper management
are at least equally important, and since animals are almost entirely dependent
upon man for providing the essentials of proper nutrition, housing, and their
total environment, animal diseases produced by chemicals have relatively more
importance in veterinary medicine than in human medicine.
Not only is the relative incidence of diseases more variable in domestic
animals, but pets and livestock are different beasts than man. Their anatomi-
cal differences are obvious. Coupled with differences in structure are physio-
logical differences in organ size and function, and in capacity and limitations
of tissue activity. Differences are also found when the biochemistry of indi-
vidual tissues and animals are examined. Enzyme capabilities in the digestive
tracts, metabolism and biotransformation systems in the liver, and transport
and other enzymatic processes throughout the body differ markedly from species
to species and between domestic animals and man. Indeed, the occurrence of
these variations is the basis for the entire group of comparative sciences.IJ»^
Of equal or more disease-producing significance than anatomical, physio-
logical, and biochemical differences are the effects of domestication and
the resulting characteristics that our animal population have developed
through years of close affiliation with man. Domestic animals have essen-
tially become creatures of habit and have maintained the specific feeding,
grazing, watering, and daily routine habits that man has imposed. Irregu-
larities in diet and routine produced by mismanagement leave the animals
with little alternative. Due to their complete domestication, animals have
become entirely dependent upon man for their total care and well-being. They
thus have become subject to man's whims, his attempts to become efficient or
"cut corners", and also to his stupidity and errors. The domestic animal is
forced to feed and be housed where man wills. Feed, water, and therapeutic
or prophylactic application of chemicals make animals susceptible to errors
in dosages, feed ingredients, faulty applications of chemicals, and general
mismanagement, with the potential for toxicity always present.
With such a wide variety of potential sources of errors due to animals'
complete lack of independence and total acceptance of their environment, it
is common to find chemical poisonings occurring under wide circumstances.
The epidemiological pattern of animal poisonings is closely related to man's
ability to properly manage his pets and livestock. The following are examples
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of some of the common animal poisonings and reflect the variety and importance
of this area to the veterinary practitioner.
Drugs and Household Products
Errors in the choice of a therapeutic compound, in its route or mechanism
of application, and in its dosage are common lapses of judgment that result in
poisoning. The faulty selection of :. worming preparation, the administration
of a new chemical by an other-than-recommended route of administration, and
the overdosage of an anesthetic are dangerous and frequently fatal errors.
The mistaking of propylene glycol for mineral oil and the administration of
1 gallon of the wrong material to horses has recently resulted in a character-
istic toxic reaction.'^ N0t only are such errors subject to frank poisoning,
but adverse reactions and the multitude of possible acute and chronic varia-
tions may also occur.
Household chemicals are a popular source for human poisonings. This is
also becoming common in veterinary medicine due to the increased number and
diversity of chemicals found and used in the home. Aspirin, vitamin and
mineral pills, birth control tablets, marijuana and drugs of abuse, disin-
fectants, and germicides are only a few of such hazardous materials.'1''2
Because types of household pets vary from birds through rodents to dogs and
cats, a wide variation in toxic response is possible. Hence, owners used to
exposing their previous pets to the usual household chemicals, may find tox-
icities developing upon the introduction of a new species of household animal.
The phenolic disinfectants are one group of commercial compound for which
this species variation is potentially of importance.
Figure 1 illustrates the normal phenolic components of urine from four
different animals. The wide variation in phenol metabolites is obvious and
reflects the variability in ability to detoxify phenolic materials. Figure 2
is the plasma disappearance of radioactive phenol in cats, dogs, pigs, and
goats following the intravenous administration of identical single doses. It
can readily be seen that the pig and goat demonstrate the ability to rapidly
detoxify and eliminate phenol from the blood. This represents not only liver
metabolism, but also excretion, primarily via the kidneys. The dog is seen
to be intermediate in its rate of plasma clearance, while the cat has a
relatively slow capability of removing the toxic phenol from the plasma. As
long as the plasma level of the toxic chemical remains high, toxicity is a
potential problem. It would further be expected that pigs and goats have
little potential for phenol poisoning, dogs would have an average potential
for toxicity, and cats would be presented with a greater hazard from exposure
to phenolic materials.
If dogs and cats are then exposed to similar doses of phenolic compounds
and their survival time measured, it can be seen that cats respond with greater
toxicity than dogs (Figure 3). Although two different dose ranges are used,
dogs had the ability to survive the phenol challenge in both cases while cats,
on the average, died in a matter of hours. When urinary excretion of the pheno-
lic compounds is measured, dogs are observed to be more capable of excreting
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the toxic material than cats (Figure 4). Thus, the capacity of dogs to meta-
bolize and excrete the phenolic compounds is apparently related to that species
ability to withstand doses lethal to cats. Although this species difference
has been experimentally demonstrated for a wide variety of household chemicals
(aspirin, cleaning fluids, petroleum products, insecticides, disinfectants), .
the phenolic dosages used to document this effect were greatly in excess of
the household exposure to which pets are subjected under usual conditions of
household use.
Nevertheless, were it not for man's faulty judgment in applying such comr
pounds directly to and around our domestic animals, toxicities due to errors
in selection of the chemical, application route, dosage, or species difference
("I think I'll bathe my cat with this new shampoo; it worked so well on my
dogs last year!"), the incidence of poisoning due to drugs and household prod-
ucts would be greatly reduced.
Pesticides ,
This group of chemicals includes insecticides, rodenticides, herbicides,,
and fungicides; the latter two have the least potential for toxicity. The
newer herbicides and fungicides are in general relatively safe, and only the
use of some of the older more toxic chemicals or exposure to organic solvents
used to carry the chemicals in their application are likely to produce poisoning.
However, rodenticides are an important group of chemicals causing animal
poisonings. Strychinine is probably the most common cause of poisonings in
dogs and is frequently used to "cleanse" the neighborhood of undesirable
dogsj»2»4»n The fact that strychnine can be purchased under the guise of
rodent bait greatly increases the hazard of poisoning. Other compounds used
for rodent control are at least equally toxic, but the limited distribution '
of such materials as 1080 (sodium monofluoracetate), ANTU (alpha-naphthyl
thiourea), phosphorus, metaldehyde, and red squill makes incidence of their :
toxicity much less than that of strychnine. Warfarin is a readily-available
compound used to control rats and mice, but toxicity is limited by the neces-
sity for repeated dosages to be ingested before poisoning usually occurs.
The insecticides are a much more complicated and diverse group of foreign
compounds.'4'20 As causes of animal poisonings, the chlorinated hydrocarbons-
and the organophosphorus and carbamate materials are hazardous. Fortunately,
effective treatments are available for the organophosphorus and carbamate '•
compounds; the chlorinated hydrocarbons are less effectively treated. The
widespread use of insecticides around large and small animals result in con- •
siderable hazard to these species. Poisoning usually occurs from accidental
exposure via spray drift or due to the intentional application of the insecti-
cide to control livestock or pet insects. In the latter instance, toxicity
may result from improper dilution of the concentrated material or too frequent
application of acceptable amounts. Both problems are diminished by users :
properly reading the labels of the respective products and abiding closely by
the specified recommendations.
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While direct toxicity to the exposed animals is a foremost concern, many
of the pesticides are capable of accumulating in feed or food supplies following
their application to the environment. Hences the widescale use of insecticides
to animals on pasture may result in hay or feedstuffs growing on neighboring
fields developing residues of these foreign chemicals. Likewise, if proper
precautions in marketing the exposed cattle are not followed, the meat and by-
products from such animals may contain high residues of the applied chemicals.
Such matters are of vital interest to governmental regulatory agencies and pro-
vide a significant concern in their efforts to protect not only animal, but also
human health JO
The government's concern with the accumulation of foreign compounds in not
only foods, but also the general environment, has resulted in the consideration
of restrictions on the use of many of the pesticides currently in use. Fore-
most in such action was the recent banning of DDT from routine usage in the
United States. This has been followed by other chlorinated hydrocarbons being
examined as a preliminary for similar restrictions. Many of the rodenticides
(strychnine, 1080, ANTU, warfarin), and some of the heavy metal materials used
as herbicides and fungicides, are being re-evaluated by regulatory agencies
because of their hazard and adverse environmental impact. Whether they will
indeed be banned from use or only restrictions placed on their applications re-
mains to be seen.
Fertilizers
The problem of synthetic materials, such as nitrates and ammonia, and
also naturally occurring organic material, such as manure, contributing to
animal poisonings may seem remote. Unfortunately, synthetic and natural ferti-
lizers are an important cause of livestock toxicoses. The most obvious situation
results from the excessive use of nitrate-containing fertilizers on crops and the
accumulation of high nitrate levels in the harvested product. These nitrate
concentrations in animal feeds can produce acute or chronic nitrate intoxication
and widespread economic lossJ,2,4,12,15,19 Even the application of manure to
fields can result in high levels of nitrates developing in plants growing in such
areas. Not only do cash crops accumulate toxic levels of nitrate, but certain
weeds, such as pigweed (Amaranthus retroflexus), are capable of building up high
levels of nitrate in their organic matrix when grown on soils containing concen-
trations of nitrates or nitrate-releasing organic matter.1>8,12,20
An instance of a vacant feedlot that had grown a lush crop of weeds and
was used to provide green pasture for cattle illustrates this problem. Within
a few hours after a large group of feeder cattle were turned into the weed-
covered feedlot, the owner found 17 cattle dead and numerous others in various
stages of toxicity. Even though the cattle were promptly removed from the lot,
approximately one-third of the animals died from nitrate poisoning. Analysis
of the weeds growing in the area revealed concentrations of nitrate as high as
4.5%.
A complicating situation is the relationship between adverse growing condi-
tions and the accumulation of nitrates in plant materials. Although levels of
nitrate may be moderate in the soils supporting grain crops (particularly corn
and sorghum) or a variety of weeds, under the influence of a drought or the appli-
cation of plant hormone herbicides, these commonly-grown plants may accumulate
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excessively high and toxic concentrations of nitrate.?»8 The widescale losses
in the middle 1950's due to livestock consuming drought-affected corn and
sorghym was largely due to nitrate toxicity. The application of 2,4-D to weeds
frequently permits these plants to develop transient toxic concentrations of
nitrate; if consumed during this temporary phase, nitrate poisoning may result.8
Natural Toxins
Toxicoses due to plants are not usual in man, but livestock and pet poi-
sonings due to a variety of poisonous plants are a significant part of veteri-
nary toxicology.3,5,7,8,9,12,13,16,17 T(.,e basi-c factor underlying most plant
poisoning problems is mismanagement.'' Livestock are frequently allowed to graze
wide areas of natural range land. When weather conditions are bad, pastures
may provide less forage than expected and limited plant material for animal con-
sumption and overgrazing frequently results. Under conditions of repeated over-
grazing, naturally occurring desirable pasture grasses due out and weeds, many
of them poisonous, take over the range. While such weeds are normally unpalatable,
hungry lives-ock may be forced to consume them and thereby become poisoned.
Although most owners recognize overgrazing and the resulting hunger that results
in their animals, mismanagement aggravates the loss of native pasture grasses
and speeds the introduction and multiplication of poisonous plants. When owners
do not provide supplemental feeding for animals on such poor pasture land, the
livestock are forced to consume the noxious weeds.
A variety of poisonous plants are available to livestock and household pets
and present hazards to their health. The cyanide-producing forages are the most
common cause of animal sicknesses due to plants. Usually the sorghyms (Johnson
grass, sudan grass, milo) are responsible for losses. In addition, arrowgrass
(Triglochin spp.), elderberry (Sambucus spp.), wild cherry (Prunus spp.), and
the pits of several common fruits (apple, peach, apricot) contain compounds
with the potential of releasing cyanide upon ingestion. Toxicities usually
result from ignorance on the part of owners who feed such plant materials to
their animals or who throw fence-row clippings into pastures to utilize the
material for forage. Adverse weather conditions and wilting frequently increase
the toxic potential from this group of poisonous plants.
Halogeton (Halogetpn glomeratus) and black greasewood (Sarcobatus vermicu-
latus) are two plants that contain high levels of oxalic acid in their plant
matrix. Although these plants are only commonly found in the ranges of western
states, the oxalic acid is an extremely potent toxin and upon ingestion combines
with serum calcium or magnesium. The clinical situation resulting from the
sudden drop in the blood level of calcium and magnesium causes large-scale acute
deaths. The loss of thousands of sheep annually in the Rocky Mountain area is
directly due to the ingestion of one or both of these poisonous plants. Only
recently a loss of several thousand sheep in one herd resulted in the erroneous
claim that the release of experimental nerve gas had caused their death. Upon
detailed examination it was found that owner-error had resulted in the sheep
consuming the oxalate-containing plants and the large-scale deaths. Since the
calcium and magnesium oxalate salts formed are excreted in the urine and become
crystalized in the kidney tubules, causing an inability to pass urine, animals
that survive the acute syndrome commonly develop renal failure.
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Locoweeds (Astragalus spp. and Oxytropis spp,} are oliier common and
characteristic causes oFTivestock losses in the western states. The plants
are not usually consumed by livestock but under adverse growing conditions
and inadequate natural forage, cattle, sheep, and horses may be forced to
consume them. Once livestock taste the plants they may develop a like for
their flavor and will then preferentially consume them, even if other feed
is supplied. Although horses and ruminant? may co^U'ne locoweeds, horses
are much more sensitive to the toxir principle's effects. Hence, as in one
recent incident when cattle and hrr-co were grazing the same pasture, hordes
develop locoweed poisoning well before cattle show even the earliest signs of
intoxication. The clinical syndrome is one of weight loss and mental derange-
ment. Animals become easily aggravated and undergo bizarre temperament changes.
Deaths frequently result from self-inflicted injuries due to running through
fences, falling down wells, or drowning in ponds or streams. The toxin has
an affinity for the nervous system and characteristic microscopic lesions are
detected in the neurons of the brain.
Selenium is a chemical found in certain types of rock and hence specific
types of soils.18 Plants growing on such soils may accumulate levels of
selenium in their plant structure varying from only a few ppm to several-10,000
ppm. While any plant growing on soils containing selenium may build up low
levels of this chemical, specific plants, such as poison vetch (Astragalus spp.)
and woodyaster (Xylorrhiza spp.), have the ability to selectively take up and
accumulate massive amounts of selenium. Some of these plants (golden-weed,
Oonopsis spp. and princesplume, Stanleya spp., for example) will only grow on
soils high in selenium; hence, they are called "indicator plants", since they
indicate the fact that selenium is present in the soils on which they are grow-
ing. Toxicity due to selenium will produce various clinical signs, depending
upon the concentration of the chemical in the consumed plants. Low levels of
selenium may result in weight loss, deformed hooves and hair loss, and the
birth of deformed young. Larger amounts of selenium cause liver damage. A
nervous syndrome, similar to that seen with locoism, commonly develops if large
amounts of selenium are ingested.
Several other poisonous plants produce such rapid death that owners may
report only that the animals were found dead. Waterhemlock (Cicuta spp.)
grows in wet areas and contains the highest toxin concentrations in chambers
just above the roots. Animals become exposed by crushing the plant in the
stream in which it is growing and then consuming the toxin-containing water,
or they may actually consume one or more mouthfuls of the plant material. The
toxin is so severe that violent muscle spasms may knock the animal off its feet
and cause death within minutes. Cattle poisoned by waterhemlock have been found
with walnut-size pieces of the plant still in their mouths.
Common oleander (Nerium oleander) is not only responsible for sudden animal
losses, but has also resulted in several human fatalities. Only a small amount
of the plant material or toxin-containing sap is required to produce poisoning.
Cases have developed from individuals consuming meats cooked using oleander
branches as spits. The toxin affects cardiac function and produces a rapid
death in all species of animals.
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Cocklebur (Xanthium spp. is a weed capable of infesting almost any
barren ground. It appears in the early spring as one of the first forms of
green vegetation. Since the plant is so common, it is fortunate that its
most potent state is during the early growth period, but unfortunately this
is just when other green vegetation is limited. Cattle and hogs may be brows-
ing pastures when early spring rains produce cocklebur sprouting. The result-
ing sprouts contain high concentrations of hydroquinone, a potent liver toxin
capable of producing massive liver necrosis and death within aifew hours. The
mature cocklebur plant is not palatable to livestock, but the burrs containing
the seeds may sprout in the fall following a warm rain. Hence, poisoning may
not only occur in the spring, but also in the fall when sprouting cockleburs
again provide lush forage for grazing animals.
The Japanese yew (Taxus cuspidata) is an ornamental plant that recently
has been shown to produce acute poisonings in,animals consuming clippings. The
plant is frequently installed around fences and animals may become exposed to
clippings or may browse the plant directly through the fence. The toxic prin-
ciple has not yet been fully defined, but horses and ruminants have been found
dead by amazed owners following access to this plant. Even though oleander
and yew are attractive plants to beautify landscapes around homes and other
structures, their toxicity provide great hazards not only for pets and livestock,
but also for children accustomed to placing foreign objects in their mouths.
Some of the lower members of the plant family, the fungi, are capable of
producing a variety of toxins. This particular group of poisons, mycotoxins,
has become a focal point for scientific investigation during the past decade.
OverHO,000 scientific papers have been published on aflatoxins alone. This
latter group of mold poisons is produced by specific strains of the fungi
Aspergillus flavus and Pen ci Hi urn spp. As with all fungi, a source of nour-
ishment and proper amounts of moisture and heat must be present to support
growth. Under suitable conditions, these fungi, and others capable of producing
toxins, will grow and in their growth processes will produce their toxins.
Hence, the toxins are products of fungal growth; the mere presence of the fungus
does not necessarily indicate that its particular toxin is also present. Con-
versely, the toxin can be present and viable fungi may no longer exist in the
sample. Mold toxins commonly develop in stored grains and on certain feedstuffs
subjected to unusual weathering or storage conditions. Although moldy feed is
usually grossly identifiable, the spoiled feed may be mixed into a ration or
otherwise offered for livestock consumption through ignorance or by intention.
Animals will usually reject extremely spoiled feed, but well-diluted feeds or
rations offered hungry cattle may result in acceptance and toxicity.
Most fungal toxins affect the liver and produce lesions varying from frank
necrosis to biochemical interference with enzymes or blood-clotting mechanisms.
Digestive track disturbances, photosensitazation, poor feed utilization, abor-
tions, and reproductive failures have been also associated with mycotoxin con-
sumption. °''2 Although cancer has never been associated with clinical instances
of mycotoxicoses, the experimental production of tumors by aflatoxins in some
laboratory animals has resulted in concern over the concentrations of this toxin,
in grains destined for human consumption. Only a few of the toxins of potential
fungal origin have presently been identified. There is no doubt that tfois inter-
esting area will continue to attract the attention of toxicologists, chemists,
and animal scientists for some time to come.
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Feed Additives
The use of chemicals added to livestock rations for the purpose of in-
creasing feed efficiency and reducing disease is a characteristic unique to
animal production. Although this practice has greatly benefited the livestock
economy, the practice is not without danger. Whenever foreign compounds are
added to feeds, the possibility of error and resulting animal or human hazard
increases. While the presence of chemical residues in human foods and their
potential contribution to adverse effects in man is of most concern to public
health officials, animals directly consuming feeds containing feed additives
are also likely to become grossly toxic. This may be due to improper mixing
of the ration, incomplete following of feeding recommendations, faulty hus-
bandry, or mismanagement. In these instances, acute poisonings result from
livestock consuming feeds to which they are unaccustomed or because the feed
contains unusually high levels of one or more toxic materials. Two such com-
mon poisonings are those produced by excessive or improper feeding of urea or salt.
The factors frequently associated with the development of urea poisoning
in cattle are listed in Table 1. Urea is a protein supplement fed ruminant
animals to provide an economical source of protein to the consuming individuals.
The production of ammonia from the urea by the ruminal microorganisms is nor-
mally followed by incorporation of the ammonia into bacterial protein; this
prtoein is digested in the intestinal tract of the ruminant and serves as a
source of nutrient protein. Under conditions of mismanagement (Table 1), the
production of ammonia becomes excessive and the rumen microorganisms are unable
to utilize the ammonia in its entirety. Ammonia poisoning then results, with
the onset of0clinical signs within minutes and death frequently following in
1-2
Salt is a necessary dietary ingredient, but in excess or in the absence of
sufficient fresh water it may become toxic.'8 Toxicity occurs most commonly
in swine, but also occasionally in cattle, due to a variety of management factors
leading to the accumulation of sodium ion in the central nervous system and
other body tissues. If the owner then discovers that water was unavailable to
the animals for a period of time, and then provides unlimited access to water,
the osmotic pressure produced by the sodium results in increased central nervous
system pressure and an acute neurological and convulsive syndrome. '^ While the
condition in cattle is somewhat more chronic and digestive signs are more promi-
nent, the underlying cause of salt poisoning is human error resulting in poor
animal husbandry practices.
Petroleum Products
A variety of oils, greases, benzenes, hydrocarbons, and other petroleum
products are used on and around domestic animals. Some are employed directly
on machinery to which livestock have access; several are utilized as solvents
for sprays and materials applied to animals; others are formulated for appli-
cation to buildings, and animals lick or otherwise contact the applied product;
or animals may directly consume the petroleum products by gaining access to
storage areas housing opened containers of these materials. In certain areas
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of the United States, oil wells and oil storage tanks provide the potential
for cattle consuming the crude petroleum product. Proper care and precautions
are frequently not taken to assure that animals are protected from exposure.
Incomplete fencings of crude oil holdings or storage areas may permit inquisi-
tive cattle to satisfy their curiosity. Ignorance of the potential toxicity
of these products leads owners to utilize various petroleums directly on live-
stock as therapeutic aids.
Petroleum products produce a characteristic sequence of clinical signs.
If applied to the skin, irritation and thickening commonly results. Photo-
sensitization is frequent, especially in white-haired or light-skinned in-
dividuals. If consumed by mouth, the petroleum material produces digestive
disturbances, may be inhaled with resulting pneumonia, and after several days
can produce liver, kidney, and bone marrow dysfunction. Pregnant animals may
abort and a poor-doing individual, continually losing weight and eventually
dying, is a usual outcome. Poisoning due to petroleum products is a compli-
cated and varied intoxication. Its occurrence could largely be prevented by
owner education and by assuring that proper precautions were taken to prevent
animal access to these materials.
Pollutants
The occurrence of air, water, industrial, and other pollutions are just
as much animal hazards as they are for humans. A good correlation may be ob-
served between animal and human toxicity problems caused by chemicals polluting
the environment. The animal epidemiology is frequently identical to that ob-
served for humans.
Air pollution usually results from industrial fumes being released to the
atmosphere, and animals in the vicinity are exposed to sulfur and nitrogen
oxides, heavy metals such as zinc and lead, hydrocarbons, and various forms of
particulate matter. Since most industrial plants are located in suburban and
rural areas, livestock grazing surrounding pastures are increasingly likely to
assume body burdens of these chemicals or to exhibit biological responses to
their inhalation. Since lead from automobile fumes accumulates in the heavier
portions of the air and in particulate matter, dogs are more likely to exhibit
signs of lead poisoning than are the adult humans living in the same environment.
Water pollution is a special problem for rural areas utilizing streams and
wells as municipal water sources. This is in contrast to larger cities that
utilize upland reservoirs many miles distant from the consuming population. The
sewage discharge of upstream communities and industrial complexes and agricultural
enterprises (feedlots, fertilization) may result in a variety of toxic materials
being present in the water used by a downstream stockman or community for drink-
ing purposes. The same waters may enter wells supplying other farmsteads or
communities.
Recent interest in nitrate concentrations in water supplies have resulted
in speculation as to the potential hazard of the continuous ingestion of low-
level nitrate waters.15 Table 2 lists the percentages of samples from selected
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Kansas water supplies with the observed nitrate concentrations. A significant
percentage (28.5%) had levels in excess of 50 ppm, and 19% had nitrate levels
in excess of 70 ppm. While the influence of nitrates on animal and human health
has only partially been defined,'5 there is little doubt that the other foreign
chemicals present in water supplies due to industrial and agricultural pollu-
tion are indeed capable of producing significant toxicity. »
Other pollutants can produce toxicities under circumstances that are fre-
quently unique to the situation. Carbon monoxide is a special problem during
winter weather in animals confined in tightly sealed quarters. Tractors or
improperly vented heating equipment utilized within such facilities may pro-
duce lethal concentrations of this gas. Antifreeze (ethylene glvcol) is a
special problem for dogs and cats because of its sweet taste.-'»^° Con-
sumption of this material when owners discharge radiators in garages or on the
ground results in toxicity due directly to the glycol or due to glycol metabo-
lism to oxalate which produces renal failure through the formation of calcium
oxalate crystals. As with most pollution problems, prevention is a matter of
education and regulation, and prophylactic efforts are immeasurably more re-
warding than the treatment of poisoned individuals.
Conclusions
The variety of foreign chemicals capable of producing animal poisonings
is almost infinite. As long as such potentially toxic materials exist and
are utilized by livestockmen and animal owners, hazards for animals, human
and domestic alike, will be a prominent concern of the health community and
of toxicologists particularly. Persons responsible for animal care must be
aware of the hazards associated with the use of these foreign chemicals.
They must be instructed and encouraged to use good judgment in the application
of these compounds on and around our animal population. Forceful and con-
tinuing education is required to assure that safe and sensible use of toxic
materials is practiced. Only if the persons handling and applying these chemi-
cals recognize their responsibility can their use be made relatively safe, not
only to the users, but also to their neighbors and to the animals in their care.
User error or ignorance is the underlying cause for most animal poison-
ings, and effective education together with the requirement for good common
sense is the prime method of reversing the increasing incidence of animal
toxicities. Chemicals are weapons—they must be recognized as such, and not
just pointed out and fired!
Summary
Animals are constantly exposed to a wide variety of foreign chemicals,
many of which are potentially toxic and some which result in clinical poisonings,
Pesticides are applied on or around animals for the control of insects and ro-
dents. These chemicals may be placed in areas without regard for accessibility
to household pets and domestic livestock. Insecticides, herbicides, and fungi-
cides are routinely and haphazardly applied to animal and environmental'surfaces
alike with apparent disregard for differences in absorptive capability. For-
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tunately, the newer herbicides and fungicides are relatively non-hazardous. :
Drugs are considered to have therapeutic effects; but the lay and professional
person's disregard for species differences and variations in recommended dos-
ages can result in poisonings. Adverse reactions may be misnomers for errors
in judgment. Failure to provide satisfactory storage facilities for animal
feeds and the improper preservation and handling of feedstuffs allow the growth
and development of a variety of mycotoxins. Ignorance on the part of animal
owners and livestockmen can result in a number of unusual and sometimes fatal'
clinical syndromes. The dependence of domestic animals and livestock upon
their owners for the total environment makes these animals extremely susceptible
to environmental pollutants. Exposure to noxious gases, irritating and hazard-
ous industrial materials and wastes, water contaminants, and casually discarded
compounds of man's own use can and frequently do result in animal illnesses and
death. Persons responsible for animals may be unaware of the potential hazard
or lack good judgment in the use of these chemicals;. Forceful and continuing
education for the safe and sensible use of all foreign compounds on and around
domestic animals and livestock is needed. Persons handling and applying these
materials must recognize their responsibility, not only to themselves but also
to their neighbors and the animals in their care.
REFERENCES
1. Buck, W. B., G. D. Osweiler and G. A. Van Gelder: Veterinary Toxicology ;
Notes. Iowa State University, Ames. 1971. ;
2. Clarke, E. G. C. and M. L. Clarke: Garner's Veterinary Toxicology. 3rd ed.
Williams and Mil kins Co., Baltimore: "^
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3. Evers, R. A. and R. P. Link: Poisonous Plants of the Midwest and their
Effects on Livestock. Special Publication 2T, College of Agriculture,
University of Illinois at Urbana. 1972.
4. Fowler, M. E.: Clinical Veterinary Toxicology. Published by the Author,
University of California, Davis. 1967.
5. Gabriel, K. L., Editor: Veterinary Toxicology. Ann. N. Y. Acad. Sci.,
III. Art. 2, (1964): 559-812.
6. Goldblatt, L. A., Editor: Aflatoxin. Academic Press, N. Y. 1969.
7. Hulbert, L. C. and F. W. Oehtne: Plants Poisonous to Livestock, 3rd ed.
Kansas State University Prin'dng Service, Manhattan/ 1968.
8. Kingsbury, J. M.: Poisonous Plants of the United States and Canada.
Prentice-Hall, Englewood Cliffs, N. J. 1964.
9. Liener, I. E., Editor: Toxic Constituents of Plant Foodstuffs. Academic
Press, N. Y. 1969.
10. Miller, M. W. and G. G. Berg, Editors: Chemical Fallout. Charles C. Thomas,
Springfield, 111. 1969.
11. Oehme, F. W.: Clinical Toxicology. In Scientific Presentations and
Seminar Synopses of_ the 39th Annual Meeting. AAHA, Las Vegas. T972.
Pp. 245-256.
12. Oehme, F. W.: Practical Clinical Toxicology. Proceedings from the Annual
Conference for Veterinarians, Kansas State University, Manhattan. 1972.
13. Oehme, F. W., Editor: Symposium on Veterinary Toxicology. Clinical Toxi-
cology, 5, (Summer, 1972): 141-302.
14. Radeleff, R. D.: Veterinary Toxicology, 2nd ed. Lea and Feblger,
Philadelphia. 1970.
15. Ridder, W. E. and F. W. Oehme: Unpublished data. 1971, 1972.
16. Schmutz, E. M., B. N. Freeman and R. E. Reed: Livestock-Poisoning Plants
of Arizona, University of Arizona Press, Tucson. 1968.
17. Sperry, 0. E,, J. W. Dollahite, G. 0. Hoffman and B. J. Camp: Texas Plants
Poisonous to Livestock. Texas A & M University, Texas AgriculturaT
Experiment Station, College Station, 1968.
18. Underwood, E. J.: Trace Elements In Human and Animal Nutrition, 3rd ed.
Academic Press, N. Y.1971.
19- Use of Drugs in Animal Feeds. Publication 1679, National Academy of
ScTences, Washington, D. C. 1969.
20. Workshop on Veterinary Toxicology. Program and Notes Sponsored by
American College of Veterinary Toxicologists, Iowa State University,
Ames, February 21-25, 1972.
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233
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50mg/kg, Dose Level
i Cot
i'»» > i i Dog
•"" Pig
•—•—•- Goat
Time, Hours
8
12
figure 2 -- Plasma disappearance of identical iv doses of
in 4 animal species.
14
C-phenol
234
-------
1 gm./kg.
L
CATS
NJ
U>
Ln
3 gm./kg.
369 12 15
24 36
TIME, HOURS
60
Figure 3 — Mean survival times for dogs and cats given 1 dose of a phenolic compound,
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Ijj
cc
ZD
o
..
o;
UJ
S5-
90-
85-
'80-
75-
70-
65-
60-
55-
50.
45
40
35
30 ^
25
20
15
10
5
DOG
(I gm./kg.
CAT (3 gm./kg.)
CAT (1 gm./kg.)
CO
CM
36
TIME, HOURS
71
Figure 4 -- Urinary excretion of a phenolic compound In dogs and cats receiving doses.
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Table 1 -^ Mismanagement and the Development of Urea Poisoning
1. Only roughage fed before urea offered
2. No previous urea fed
3. Switch to high urea ration suddenly
4. "Bully cattle" hog feed
5. Cattle unusually hungry, overeat
6. Feed instructions not followed
7. Accidently fed wrong mixture
8. Improper or incomplete feed mixing
237
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Table 2 -- Percentage of Water Samples Analyzed with Various Nitrate Concent'--^ .ons
238
0-10.9 41.9
11-19.9 13,4
20-29.9 7.3
30-3^.9 5.0
40-49.9 3.9
50-59.9 7.3
60-69.9 2.2
70 & over 4^9,0
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