c/EPA
              United States
              Environmental ?'0taction
              Agency
              Office of
              TOXIC Substances
              Washington, DC 20460
EPA-560," 2-73-003
April 1980
                Substances
Toxic Substances:
              A Brief  Overview of
              the issues Involved

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                         TOXIC SUBSTANCES:

                         A Brief Overview

                               of the

                         Issues Involved
(This  publication  was  prepared,  under a  Grant from the  U  S
 Environmental  Protection  Agency,  by  the New  Jersey  Public
 Interest Research Group  (NJPIRG)  in  cooperation  with  the
 New Jersey  League of  Women  Voters)

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                               CONTENTS


INTRODUCTION:  Toxic Substances: A Brief Overview                I

BIOLOGY:  DNA and All That.                                      9

CHEMISTRY:  Name That Toxic!                                    13

PHYSIOLOGY:  How the Toxic Substances Sneak Past Your
             Skin and Liver.                                    15

ECOLOGY:  Where the Toxics Hide in the World.
          Toxics Moving and Influencing the Environment.        18

ANALYSIS:  Risk: A Very Theoretical Solution to a Very
           Real Problem.                                        20

LAW AND TOXICS                                                  23

AN EXTENSIVE BIBLIOGRAPHY                                       26

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                             INTRODUCTION


                           TOXIC SUBSTANCES

                           A Brief Overview

                        by Robert Dahl, NJPIRG
     This pamphlet contains an introduction to some of the basic issues
involved with the control of toxic substances.  It is hoped that anyone
unfamiliar with the field will find it easily understandable, but it is
suspected that specialists in related fields will  find it somewhat brief:
It is intended to be a starting point, not the final  word.  There is
suggested additional reading, which is also general in nature.  The pam-
phlet offers:  Useful  definitions of pollution and toxics; A categoriza-
tion of toxics by both chemical properties and effects; A review of the
problems in detection  and identification of low-level ubiquitous toxics;
and perhaps most important, an exposition that toxics are not a new look
at an old .problem, but are a whole new problem.

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Toxic Substances - A Fundamental Change in Pollution Problems


     Man's pollution of his environment is not new—it may, in fact, be
intimately associated with the species known as "intelligent man".  When
man began to make tools and purposely alter his environment, he became a
generator of pollution.  In the Introduction to the Reference Encyclo-
pedia of Ecology and Pollution, Rene Dubos states that "contrary to gen-
eral belief, (pollution) problems do not result from the fact that
modern man suddenly acquired wasteful and careless habits...The arti-
facts made of stone, ivory, or pottery which litter prehistoric sites
are the equivalent of gadgets, plastic containers, and aluminum cans
with which we litter our landscape.  There is no evidence that we are
more wasteful than our prehistoric ancestors...what is certain is that
our wastes and pollutants are chemically different from those of the
past".

     Before the  Industrial Revolution, most wastes were easily biode-
graded because they were made from 'natural1 materials.  These materials,
such as sewage, wood, and leather, had been present in the environment
for a long time.  Bacteria, insects and other decomposers were pre-
adapted (from ages of decomposition of bio-materials  in normal trophic
interactions) to break down these wastes.   Indeed, care must still be
taken to keep decomposers out of the wooden frame of a house, or a
favorite pair of leather shoes.

      In the last hundred years, however, there have been great advances
in knowledge on  nearly all fronts, particularly  in our ability to use
and manipulate chemical substances to produce materials with nearly any
desired properties. .Certainly man has benefited greatly from this
ability, but as  these products are produced, distributed and consumed,
their ultimate destination is a return to the environment at large.
Many of these substances and  their associated byproducts are totally new
to the world, and there are,  therefore, no decomposers equipped  to
handle them.  Some substances are elements, such as metals, and are
simply not decomposable.  Since these substances are  continuously pro-
duced, and decompose slowly if at all, they accumulate.  As they accumu-
late  they may affect the functioning of ecological systems, including
the ecology of human beings.  Rene Dubos continues:   "like other organisms
in nature, human beings are ill-equipped biologically  to deal with many
of the man-made  substances produced  by modern technology...We have no
instinct or organ to warn us  of the  dangers that  lurk  in an invisible
beam of radiation or In toxic substances which are tasteless and odor-
less  in the concentrations commonly  found  in  the  so-called normal envir-
onment of technological societies".

      The goal of controlling  man-made toxic substances  in our environ-
ment  cannot  be  thought  of as  part of a  'back  to  nature' movement, which
implies that we  were once cleaner  than we are now.  Man has always been
a  polluter;  in  the past he changed the degree or  amount of decomposition
necessary,  today he  Is  changing the  kind of decomposition necessary.
Nature  is not equipped  to do  that decomposition,  so man must do  it him-
self.  This demands a  fundamental change  in man's philosophy and  relation
to  his environment.

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Pollution vs. Toxicity - an attempt to define terms.

     The words 'pollutant' and 'toxicant1, two terms for substances
which can be toxic, are often used interchangeably. This is not surpris-
ing because both words have a broad range of meaning in general use.  It
is helpful and realistic, however, to assign at least somewhat more
exact meanings to these words—even though these definitions must necess-
arily overlap to some degree.

     When we speak of a toxic substance, we are speaking of any material
which will inhibit or destroy the normal functions of living tissues
when that tissue Is exposed to a specific dosage for a specific duration.
This inhibition of function may occur very quickly or may take several
decades to develop.

     We may speak of the air being polluted with high levels of carbon
dioxide, even though this compound is normally present in low concentra-
tions, and is vital for photosynthesis  in green plants.  A lake may be
polluted by an over-supply of phosphates, whereas  if^all the phosphate
were removed the lake would become as lifeless as  the rock beneath  it.
This is perhaps the best definition of a classic pollutant:  a substance
which is essential and beneficial in nature, but is harmful in elevated
concentrations. Pollutants generally become toxic when concentrations
reach  the parts per million  (ppm) range.

     Toxicants may be regarded in the same light,  but the range of
concentrations which are not harmful becomes vanishingly small, or
disappears altogether.  Toxicants are active in the parts per billion
(ppb) range.
Chemical Categories of Toxics

     Host toxic substances can be placed  into one of several general
categories on the basis of their chemical properties.  These categories
overlap widely.

     Metallic elements and compounds—such as lead, mercury, and cadmium.
Since metals are elements, they are not biodegradable.

     Small organic and inorganic molecules—such as nitrates, sulfur
oxides, and carbon monoxide.  Most of these are normally present, but
become problems at higher concentrations.

     Larger organic compounds—such as benzene, PCB's, phthalates, and
most pesticides.  These compounds are not normally present, and very low
concentrations may be harmful.

     Radioactive wastes—while not directly entering Into and disturbing
chemical reactions, do exert a chemical effect.  As a radioactive iso-
tope of an element decays into a non-radioactive isotope, it gives off a
high-energy particle which may Interact with many molecules along its
path.  The interactions generally Impart  some energy to the molecules—
allowing them to undergo reactions which  are not possible under normal
condi tions.

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     Thus, most small organic and inorganic compounds are pollutants
which may become toxic by virtue of elevated concentrations, while
metals, large organics and radioactive isotopes can be viewed as toxic
substances at almost any concentration.
The Effects of Toxics

     When the concentration of a toxic substance becomes high enough,
through  intentional or accidental release or assimulation,  it may cause
immediate (acute) effects.  These unfortunate events have the benefit of
facilitating the correlation of a specific toxin and its symptoms.  More
often, however, the toxin  is present  in  low  (but still active) concentra-
tions, which may not cause symptoms to appear immediately.  This  is
known as  'chronic1 exposure, and the  delay between exposure and the
appearance of symptoms  is  called the  latency period.  The phenomena of
chronic  exposure and a  latency period make it very difficult to corre-
late specific symptoms with specific  chemicals.  Extensive  testing may
be needed,  in which the chemical is administered in what  is judged to be
an acute dose (to bacteria or mice).  Even if toxicity  is established,
the exact mechanism of  toxicity may be difficult or  impossible to
elucidate—either due to our  lack of  complete understanding of the
chemical  interactions of  life, or due to the non-specific action  of  the
toxin.   Toxins are generally assigned to one or more of  the following
categories:

     Mutagens - Cause random changes  in  the  information  stored  in  the
DMA, the genetic material  of nearly all  living  things.   While cells
possess  systems for the correction of mutations  (indeed  some cells have
systems  for  causing mutation—with vital functions  protected), once  the
mutation is  complete  the  information  is  changed.   As with any  finely
tuned  system, a change  is  more  likely to be  harmful  than good, although
 it  is  often  neutral.

     Carcinogens  -  cause  the  unrestricted proliferation of  abnormal
cells  which we  call cancer.   Mechanisms  seem to be mutagenic  in  some
 cases,  but  are  largely  unknown.

     Teratogenlc  -  causing birth defects and abnormalities.   The  classic
 example is  the  sedative drug  Thalidomide, which was identified  as the
 causative agent in  a  number of similar  deformed births.  Thalidomide was
 subsequently shown  to fae teratogenlc, carcinogenic and  mutagenic.

      General toxins - which may affect  various  life functions.   A good
 example Is  Mercury, which Is known to react  with the sulfhydril  groups
 in proteins.  These groups play a major role in the three-dimensional
 configuration of large protein molecules.  The  biochemical  activities  of
 these proteins are defined by their ability  to  recognize other molecules
 by their three-dimensional characteristics.   Changes in the shape of the
 protein may reduce or destroy that ability.   General toxins may cause
 anything from discomfort, headaches and  indigestion, to behavioral
 changes, neurological damage and death.

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 Problems  in  the  Detection  and  Identification  of  Toxics.

      A  partial  list  of  problems  likely  to  arise  in  any  investigation  of
 a  suspected  toxic  chemical  includes:

      -  Toxins may be active  in  concentrations too  low  to  be  detected by
 qualitative  analysis.   For  example,  it  is  not clear whether hexachlor-
 ophene  is  itself toxic, or  is  laced with minute  undetectable  impurities
 of the  ultra-toxic dioxins.

      -  Latency  between exposure and expression  of  symptoms makes  it
 difficult  to correlate  a specific  toxin and  its  effects.   For  instance,
 asbestos usually takes  20-30 years to show its effect.

      -  Chemically related  compounds may have nearly  the same  toxicity,
 or very different  toxicities.  This makes  it  very difficult to predict
 which chemicals  are  likely  to  be dangerous.

      -  Synerglstic  effects -  two  toxins (or  even non-toxins) may  inter-
 act  in  such  a way  that  they are  far more toxic when together  than would
 be expected  on the basis of their  toxicity when  present alone.

        Resolution - There are many chemicals in use  today to which
 people  are commonly  exposed.   This makes correlation  of specific chem-
 icals to specific  effects even more difficult.

      -  Natural  toxification - relatively  non-toxic compounds may be
 made  more  toxic  by the  body's  detoxification  systems.  Tom Eisner, a
 biologist at Cornell University, tells an  interesting "natural history"
 story on this subject.  Many plants produce toxins  for protection against
 insect  herbivores.  Many insects,  in turn, have  evolved a detoxification
 system  which allows  them to eat  the toxic  plants.   He has found that
 some  plants  now  produce non-toxic chemicals which are rendered toxic  by
 the  insect's already existing  detoxification  mechanism.

        Ignorance  of toxic mechanisms make scientific study difficult.

      -  Scientific testing procedure is designed in such a way that
 false results are  given with a certain frequency (there is a trade-off
 here  between having tests sensitive enough to find  small yet real  diff-
 erences; and avoiding false positive results  due to normal random varia-
 tion  in results) .

      -  Toxics are useful  in some cases, and  are produced because people
 need  or want them or things they help produce.  Hexachlorophene is an
 excellent example;  It was widely used as an anti-bacterial cleanser,  but
was found to cause brafn damage when used  in  high concentrations.   It
 is, however, excellent  in fighting staphylococci  in specific situations.
 The decision was made to classify hexachlorophene as a drug,  so that  it
may only be used when the benefits out-weigh  the costs.  It is still
 used  to fight staphylococcf, But not diaper rash.

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Decision Making:  What Level of Risk is Acceptable?

     - In the decision process to determine whether the use of a sub-
stance constitutes an unacceptable risk, traditional methods of cost/
benefit analysis break down, because important parameters are not well
known.  For instance, there is a 'zero/infinity1  paradigm, meaning that
the probability of an event is near zero, but the potential cost of that
event approaches infinity. A good example of this is the problem of
accidental nuclear reactor core meltdown—which would release large
amounts of radioactive material into the environment.  Advanced tech-
nology can reduce the chance of this happening to near zero, but the
potential cost remains high (and may even get higher, since an ever more
costly piece of equipment is destroyed).  Cost benefit analysis talks in
dollars and cents, but it is difficult to estimate the value of such
things as clean water, pleasant surroundings, good health, and a clear
night sky.

     The presence of toxic substances  in the ambient environment is a
problem of our entire society.  At present, however, small segments of
the society are making the significant decisions  (or lack of decisions)
for the entire society.  Scientists evaluate the effects of toxics, and
may make recommendations regarding decisionmaking, but the actual power
to make and enforce decisions  rests with various government agencies.

     As mentioned above, the usual method of governmental decisionmaking
is cost/benefit analysis.  Costs and benefits of an action are estimated,
and if the benefits exceed the costs,  the action  is carried out.  This
system sounds extremely simple, and it can be.  Problems generally
arise, however, because to facilitate  comparison both costs and benefits
must be translated into a common currency:  the arbitrary units of
dollars and cents. There may be wide disagreement on the value assigned
to a certain cost or benefit,  and special interest groups may seek to
reduce or  inflate the assigned values  in an attempt to tip the scales in
their favor.

      In the regulation of toxic substances, cost/benefit  is reduced to
the concept of "acceptable risk".  Actuarials determine  the level of
risk which the population seems to accept  (e.g. driving  cars), and
assumes that comparable environmental  risks will be acceptable.  One
major flaw in this system is that there  is a large data  base for accur-
ate estimation of the  risks while driving a car, but little such data
exists for the estimation of environmental and public health risks.

     The other major weakness  of this  approach is that there is rarely
an opportunity  for the general public  to express  its views on the  level
of risk  they are willing  to accept.   Ideally, a well-informed public
should be  the primary  decisionmaker  in regard to  the risks to which they
wi11  be exposed.

      Assuming that these  problems can  be  ironed out of the process,
there  remains a  large  problem  In the validity of one of  the primary
assumptions of  cost/benefit analysis.   This  is the assumption that
relationships are continuous—meaning  that a small change  in the con-
centration allowed by  regulation would cause only a small change in the
costs of maintaining  this  level, and a corresponding small change  in  the
benefits expected.   This may not always  be  the case.  For example, in a
study on  the carcinogenic effects of  tobacco smoke  (thus  the study had a

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large data base, and therefore reliable figures), the following results
were found relating exposure to carcinogens (# of cigarettes per day)
with relative risk:
                             RELATIVE RISK

                                                       Cancer of
# Cigarettes                  Lung Cancer              Esophagus

Non-smoker                         2                      I
 1-10                           12                      3
11-20                           26                      3-2
21 - 30                           39                      3.7
31 - kO                           1*5                      3-8
i»l +                              60                      3-8

(From Wynder and Stellman, 1977.  Cancer Research 37:A608-22)
     With regard to lung cancer it is clear that the higher the exposure,
the greater the risk.  With cancer of the esophagus, however, the results
are very different.  It appears that any non-zero level of exposure  is
equally bad.  It is not important here that the absolute fi-gures for
cancer of the esophagus are lower than the figures for lung cancer,  the
point is that according to this study, there is no completely safe lower
limit. When one considers that living in the Boston-New York-Philadelphia
area has been estimated to be equivalent to smoking on the order of  10
cigarettes a day, the implications on public health are staggering.   It
is suspected that many toxic substances are in a way similar to the
effect of smoking on cancer of the esophagus--no level of exposure,
other than zero, can be said to cause no increase in the incidence of
detrimental effects.  Under these conditions the previously mentioned
assumption that a small change in concentration will cause only a small
change in cost/ benefit, simply is false.  Small changes at high levels
will have little effect—drastic reduction of exposure to near zero will
have a drastic effect.

     It is important to note that many decisions as to level of accept-
able risk have to be made with much  less data than is available in the
case of cigarette smokers.  Rather than wait for future date (which may
be very long in coming), these decisions must be made to limit poten-
tially damaging exposure.

     Decisions on toxic substances will still be made by government
agencies, but the Issues must be decided using different criteria,
including input from the society at  large (e.g. non-special interest
groups such as the task forces in this program).  In this way society
will have real influence in deciding these very real issues which have
derived from one of man's ancestral  habits, and his new-found knowledge
and prosperity.

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Suggested Reading


Chemical Villains:  A Biology of Pollution

     James W. Berry, David W. Osgood, and Philip A. St. John.  The C. V.
     Mosby Company, St. Louis, 197*».

     Highly recommended.  This book contains excellent and understand-
     able short review of ecosystem theory, biochemistry, and anatomy/
     physiology. The second half of the book contains no-nonsense  infor-
     mation on a wide variety of Toxics.  180 pages with 89  illustrations.

North American Encyclopedia of Ecology and Pollution, edited by Wm.
     White Jr. 6 Frank J. Little, Jr., North American Publishing Co.,
     Philadelphia. 1972.

     A collection of articles by various specialists; worth  skimming
     through.  Rene Dubos1 Introduction is excellent.

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                                BIOLOGY

                           DNA AND ALL THAT

Introduction
     In the last thirty to forty years our knowledge of the workings of
living systems has mushroomed from descriptive hand-waving to an intimate
understanding of a few of the basic bio-chemical systems of life itself.
The pollution of living systems with various toxic substances has in
some cases been shown to have specific adverse effects at specific
points in these systems.  It is important that we have some understand-
ing of these systems at the molecular level, so that we better under-
stand the effects of toxic substances on our ecosystem in general, and
on ourselves in particular.

     In the first half of the twentieth century, there was intense
activity in the scientific world.  It was obvious that life required
large amounts of information to be stored inside each cell.  This is
apparent when one considers that every human being starts life as a
single cell, and In the first nine months of existence grows into a
completely functioning, though nearly helpless, individual.  The amount
of information necessary to orchestrate this development must be impress-
ive, and nearly all contained in that single, first cell.

     It was known that certain parts of the cell called chromosomes are
responsible for the transfer of genetic information, but chromosomes are
made of both DNA (deoxy-ribo-nucleic acid) and proteins.  The question
was:  Is the information stored in the DNA or in the protein?  Circum-
stantial evidence suggested that the proteins were more likely to be the
correct answer.  This turned out to be dead wrong.

     It has been found that the DNA contains the genetic information,
and that this Information is translated into the structure, and thereby
the function, of proteins.  The story of the flow of this information  is
a beautiful example of the elegance and simplicity of nature.  The dis-
ruption of this system by toxic substances has widespread and irrever-
sible impact on all living things.

The Structure of DNA

     Each DNA molecule is like a long chain with spurs.  It has a long
backbone of repeating units, and each unit in the backbone has a side-
group (a so-called nucleotide base) projecting from it.  There are four
possible side groups: Adenine, Thymene, Guanine, and £ytosene (remember
the initials, not the names).  DNA molecules are virtually always pres-
ent in pairs, due to weak but significant interactions between the side
groups. Adenine prefers to be near Thymene, and Guanine pairs with
£ytosene. Thus the typical structure of a DNA molecule, or rather a pair
of DNA molecules, is with their projecting side groups aligned with A
paired with T, and G paired with C.  The two backbones are on the out-
side. The two backbones have some  'spring1 in them, which makes them
twist around one another.  Thus the pair of DNA molecules can be visual-
ized as a twisted ladder, with the rungs being the side groups project-
ing inward and joining, and the sides of the ladder as the backbone of
repeating units.  The two molecules are 'complementary1 to one another;

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that is, if one has the sequence A T G C, its neighbor will have the
sequence T A C G.  This complementarity gives DNA one of the most
important characteristics, the ability to replicate itself.

DNA Rep Iicat ion

     DNA replication is schematically a very simple operation, the two
strands of DNA are separated, and a new complementary mate is assembled
for each.  Both of the new ladders are exactly identical to the original.
This has been proven by the very clever use of strands of DNA which are
'marked1 with radioactive side groups.  The marked strands can be follow-
ed through several generations, and in each case the old DNA material  is
divided evenly between the two 'daughter1 cells.

     The fact that DNA can be replicated implies the possibility that  it
may be replicated incorrectly.  An incorrect replication of a DNA mole-
cule is known as a mutation.  A mutation may be the substitution of one
side-group for another, say A is replaced by G; or whole sections of DNA
may be moved from here to there as the backbone is broken and repaired
incorrectly.  Sections of DNA may even be lost completely. Many toxic
substances are known or suspected to cause mutations.  Since virtually
all living things use the DNA system, a substance which causes mutation
in one organism  is likely to cause mutation  in many other organisms.
Once a mutation  is complete, the changed DNA is replicated as though it
were correct, since the cell has no way of knowing that it.contains an
error.  These errors may have profound effects on cell systems, includ-
ing causing cancer.  This is because the sequence of A T G and C side
groups on  the DNA strands is the clever yet  simple code used  for the
storage of the information necessary  in protein synthesis.

Protein Synthesis

     Protein, like DNA, consists of a  long chain of repeating units. In
proteins there are twenty side units called  amino-acids - we will not
worry about their names.  Proteins are not paired to form  'twisted
ladders',  like DNA.  Proteins play a wide variety of roles  in all cells.
They may be structural, such as  the proteins in muscle  fibers; or pro-
teins may  be  functional,  such as the digestive enzymes.

     The recommended daily  intake  (RDA)  for  protein  is about  ^0 to 50
grams per  day.   This protein enters the  body as  long-chain  proteins
produced fay some other organism, such  as a corn plant, a wheat plant,  or
a  chicken.  These  long-chain proteins  are of no use to a human being,  so
the digestive enzymes  tear  the protein back  down  into  its  individual
amino-acid building blocks.  The most  facinating part of this story  is
the use of the  Information  In  the  DNA  to take  these amino-acid building
blocks  and put them together  In  a  new  way so that they will  form a
protein which will be  helpful  to a human being.

     The first step In protein synthesis is  the generation  of a DNA-like
molecule called  'messenger-RNA1  Cor MRNA for short: RNA,  rjbo-nucleic
acid).   This  Is  done by a system almost  identical to  that  used  in DNA
Feplication.   First, the  two  strands  of  the  DNA  separate  (probably not
                                   10

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completely from end-to-end, only  in  the section  that  is  going  to  be
transcribed  Into RNA), but  this time only one  side  is  replicated,  using
RNA building blocks  rather  than DNA  building blocks.   The MRNA strand  is
peeled off, and the  DNA strands are  repaired.  Thus the  DNA  is used only
as a template for making messenger-RNA.  The newly-made  MRNA strand is
then transported to  another part of  the cell,  carrying the  information
from the DNA.  This  Is why  it  is called Messenger RNA.

     Now it gets a bit more complicated.  A  large protein structure
known as a ribosome  accepts the MRNA strand, and with  the help of  energy
and special "transfer RNA  (called tRNA, of course), the  ribosome  gener-
ates a protein.  To  do this, the ribosome uses twenty  kinds of tRNA
molecules, one for each of  the twenty kinds of ami no-acids which will
make up the protein.  Each of  the twenty tRNA  molecules  binds  to  one
specific amino-acid, and will  also bind to a specific  sequence of  three
of the side groups on the mRNA.  As one tRNA/amino-acid  complex binds  to
the beginning of the mRNA,  the ribosome traps  it there and waits.  When
another tRNA/ amino-acid complex binds to the  next  three side  groups on
the mRNA, the ribosome moves forward three side  groups,  joins  the  ami no-
acids together, and  lets one of the  tRNA's escape.  The  ribosome  contin-
ues to shift down the mRNA molecule, three side-groups at a  time,  adding
another amino-acid to the growing protein with each shift.   Finally the
ribosome reaches a special combination of three  side groups which  means
STOP.  The ribosome  then releases the string of  ami no  acids  it has
generated, and releases the mRNA.   It seems unbelievable, but  it  is
true.

     To summarize protein synthesis:  a section  of  DNA is transcribed
onto mRNA; the mRNA  is translated three units  at a  time  by  ribosomes
using tRNA/amino-acid complexes; the ribosome  uses  cellular energy
sources to join the  amino-acids together to form proteins.  Thus  each
three side groups of the mRNA  (and therefore of  the DNA  itself) corres-
pond to one of the amino-acids In a protein.   A  mutation, or a change  in
the DNA will cause a change in the sequence of amino-acids  in  a protein,
which potentially alters the structure of the  protein and its  ability  to
function properly, since the structure of a protein and  its function are
very closely related.  The relationship between  protein  function and
protein structure Is the final concept needed  to understand the signif-
icance of mutations  in the DNA.

Protein Structure

     When a protein  Is produced by the process outlined  above,  it  is
only a long string of amino-acids.  The various  amino-acids  in  the
string have different chemical properties.  For  example  some of them are
'oily1 in nature.  These are called  'hydrophobic1 (literally 'fear of
water1), because they tend to avoid being in direct contact with water
(much the same way that 'oil and vinegar don't mix1).  Other groups are
hydrophyl1Ic, or 'water loving1.  These differences are  very important.
In the environment Inside the cell, which Is mostly water, the  protein
automatically bends  and folds back on Itself in  such a way that as many
as possible of the' hydrophyl1ic amino-acids are on  the outside.  Factors
which fine-tune the  folding of the protein are temperature, acidity, and
the concentrations of certain substances Inside  the cell.   If  conditions
are correct the protein will contort itself in a very specific way, and
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by virtue of its shape and surface, the protein will become 'active' -
that is, it will have the ability to attract and hold certain specific
smaller atoms or molecules.  A good example is blood hemoglobin, which
may hold either oxygen or carbon dioxide to move these gasses back and
forth between the body and the lungs.
     It now becomes apparent that a mutation in the DNA will mean the
change in the activity of the protein, through the following course of
events:  Mutation causes change in the sequence of side groups in the
DNA, which causes a change in the side groups in the mRNA, which causes
a change in the folding of the protein, which may change the ability of
that protein to attract and hold molecules, which means a change in the
ability of the protein to do its job.

     So, where do Toxics fit In with all  of this?  This is certainly a
very complex system, and toxics may have their adverse effects at any
point  in the system.  They may cause mutations to occur more frequently;
they may cause breakdowns in the process which regulates when each
section of DNA is used; they may alter the inner cellular environment in
such a way that proteins do not have their normal shape and therefore
the proteins will not function properly;  in essence, the system is so
delicate that toxic substances can interfere at any level and have an
impact on the everyday functioning of this system - a system we call
life.

Conclusions

     Today, it is universally accepted that the DNA carries the genetic
information and that this information is expressed through the synthesis
of proteins, which act as the structural  elements for various tissues,
and as enzymes which take part in virtually every cell reaction.  Every
animal, plant, fungi, bacteria and algae on the earth relies on the
integrity of this system.  Man, who is certainly one of the most extra-
ordinary examples of this system, shares unbreakable ties with every
living thing through this common chemistry of life.  He is, however,
unique in his ability for self-awareness and the accumulation of know-
ledge.  Man must turn this self-awareness and knowledge to look on his
actions with a more comprehensive viewpoint.  The problem of toxic
substances in the environment is conspicuous- In its urgency and in its
threat to the very foundations of life itself.
                                  12

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                               CHEMISTRY

  NAME THAT TOXIC!  - A step toward understanding the Chemist's Jargon


     One of the problems that people face when trying to help solve the
toxics problem is the exotic jargon of chemists.  Chemists are, of
course, not the only group with their own jargon:  lawyers, bureaucrats,
psychologists, artists, carpenters, plumbers, and almost any other
special interest group develop their own private channel to talk on by
the use of specific words.  In the final analysis they are all the same;
a carpenter speaks of headers, liners, jacks and sills, while a chemist
talks about carbon chains, hydroxyl groups, benzene rings and  inorganic
salts.  There are many chemicals with names; and to make matters worse,
there is often more than one name for the same chemical.   It would,
therefore, be senseless to list and explain even a small fraction of
them here.  Instead, we offer a short introduction to chemical termin-
ology.

     Everything is composed of atoms, and an atom is mostly empty space.
Each atom has a small heavy core  (nucleus) made of Protons and neutrons.
A number of light electrons are in orbits around the nucleus.  The
protons in the nucleus have a positive charge, and the electrons have a
negative charge (neutrons have no charge).   If an atom has as many
electrons as protons, the atom has no net charge as a whole.   If there
is a shortage or surplus of electrons, the atom will have a net charge,
and may be called an  ion  (say eye-on).  The condition of the electrons
determines the chemical properties of an atom -  in fact all of chemistry
may be reduced to the Interactions of electrons of one atom with the
electrons of another atom, (if there  is a change in the number of pro-
tons  in the nucleus,  the atom changes very severely, and becomes a
different element - for example in nuclear reactors Uranium splits into
other  lighter elements such as  Iodine, Argon Strontium, and others.  The
altered number of protons  in the  nucleus effects the electrons orbiting
around it, and thus changes the chemical properties.  A change  in the
nucleus is a drastic and  relatively  rare event  in nature.)   If  there  is
a change  in the number of  neutrons  in an atom,  the atom does not change
to another element, but becomes a different  isotope  (literally means
'same place1) of the  same  element.   For example  carbon normally has a
total of  12 protons and neutrons  \n  Its nucleus  -6 protons and  6 neutrons,
A certain percentage  of carbon atoms  have a  total of  1A protons and
neutrons, 6 protons  (which makes  It  act  like other carbons), and 8
neutrons.   Isotopes are Indicated  by  the chemical symbol with  a number
in the upper  right hand corner, for  example  Carbon  U  is written
others are  L,1 and 1^33  Uay "fodine-one-thirty-one", and "Uranium  two-
thirty-eight1^ or Just "you-two-thi rty-eight") .

     Atoms  may be bonded  to one another  to form molecules.  Air  is
mostly molecules of Nitrogen  (two  Nitrogen atoms bonded  together) and
Oxygen molecules  (two atoms of Oxygen bonded  together).  Water is a
molecule made up of one atom of Oxygen and two atoms of  Hydrogen.  A
method of shorthand for writing how many atoms of each element are in a
molecule has been established.  The chemical  symbols for the elements
are used, with a number in the lower-right corner to indicate how many
atoms of this element are present.  For  example water  is written H^;
molecular Oxygen  is 0   ;  and sugar  (glucose)  is C^-i^g' which means


                                  13

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six carbon atoms, twelve hydrogen atoms,  and six oxygen atoms.   Note
that this system does not tell  you how the atoms are hooked together.
Obviously there are many ways to arrange these 6+12+6=2^ atoms  - much
the same way that different bricks can be combined in different ways to
produce walls, window sills, and front steps.  For example, wood is
chemically very similar to sugar and starch, but the small differences
make it impossible for animals to digest wood.

     One of the most important properties that characterizes a  substance
is its ability to dissolve in various types of liquids.  For example,
thanks to TV ads, everyone knows that oil and vinegar don't mix—Why is
this true?  The problem is that vinegar is a "polar" substance, which
means that each molecule acts like a tiny magnet.  All these magnet-like
molecules attract and repel one another, and line themselves up.  Water
is polar, so other polar substances will dissolve in it rather  easily.
When one attempts to mix a non-polar substance such as oil in water, it
does not work because it is difficult to get the water molecules to
separate to let the oil molecules in between them.  There are different
degrees of polarity and non-polarity, so  it  is often possible to get two
substances which will dissolve temporarily, and  then separate later as
the polar molecules slowly attract one another,  as is the case with most
salad dressings.  If one chooses the ingredients correctly, and mixes
properly, the ingredients will stay dissolved.   Examples would be cold
cream or first-aid ointment.

     The interactions of atoms and molecules are really what chemistry
is all about - and when you think about  it,  it becomes obvious that
these  interactions depend on how two substances  react when they are
close  together -  in fact how they  'react1 when they  touch one another.

     There are several other concepts which  could help to  understand the
chemist's jargon, but you probably already own one of  the  best  resource
books  in your own home.  For example - how do you find out what trichloro-
fluroethylene really  is?  Divide and Conquer—and get out  the dictionary!!
By  looking up each section of the chemical name  you  can get a better
idea of what  the  substance  Is made of.  Many modern .dictionaries give
definitions for  the more common  chemical  substances,  so it  is often
possible to look  up  the word directly.   If you  really get  interested,
many  libraries have  books on Chemistry -  and  a good  high-school text
will give  the basics  clearly and  in enough detail that you will be  able
to  hold your own  and  understand  most of  the  chemical  buzz-words.

      In conclusion,  Chemistry  is  like any other  special subject  in  that
 it  has it's own  jargon.   It  Is worth  learning a  bit  of  this jargon,  and
 Is  really  no  harder  than  learning what a  fugue  sounds  like, or  an  Im-
pressionist painting  looks  like, or even  how to  dance  Disco.   Chemistry
may not make  the best cocktail  party  conversation,  but  if  you wish  to
communicate with the  various groups  involved with toxic substances,  your
group  will  be more effective and less  frustrated if  you can understand
some  of  the basic Ideas  behind  the  big  buzz  words.   Probably the best
strategy  Is to  recruit  a  Chemist or  Chemical  Engineer, or  study up  on
 the subject - either  way  it will  be  necessary to make  more detailed
 investigations of various  substances  as  they become  important  to you.
Hopefully,  there will  be  effective  communication between  groups, so  that
 there will  not  be duplication of research efforts.
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                              PHYSIOLOGY

                    How the Body Deals With Toxics
     There are three major ways toxic substances can enter the body:
through the skin, lungs, or digestive tract.  A specific toxic substance
may enter the body and do damage through one route, say the digestive
tract, but may be unable to enter by another route, say the skin.   It is
useful to have some understanding of how and why toxics are able to
penetrate the barriers which attempt to keep the body separate from the
outside world.

Ingest ion: Food For Thought

     The material which makes up the eyes with which you read this page,
and the brain with which you understand it, had to come from the food
and water that you ate.  Unfortunately, this food and water is becoming
more and more contaminated with various toxic substances.

      If a toxic is present in a very high concentration - and the body
has the ability to sense Its presence - one of several mechanisms may
come  into play to help reduce exposure.  The taste buds may reject  the
substance and motivate the person not to swallow - or if the substance
has been swallowed, the esophagus may be activated to perform the vomit
reflex - which is basically a long swallow  in reverse.  Unfortunately,
however, many toxic substances do not stimulate either of these  re-
sponses -and the food  is consumed without any immediate problems.  As
the toxic substance passes through the digestive tract, one of several
things happens to it.  In some cases the toxic may be unable to  pass
through the walls of the intestine - and so the toxic is carried along,
and ultimately is eliminated with the feces.  In this case there prob-
ably  is no harm to the body, though it may  irritate and cause problems
such as cancer in the  lining of the stomach, intestine, or rectum.  (it
is important to note here that the same substance may be harmful if
inhaled or applied to  the skin rather than eaten.  For example,  you can
eat four packs of cigarettes a day if you like - but don't inhale them!),

      If the toxic in the food or water is able to pass through the wall
of the intestine, there is the potential for greater harm. As substances
pass through this wall, they enter the blood system, and are carried to
the liver.  The liver may be visualized as an active filter system which
has the ability to alter some substances in such a way that they become
either more useful or  less harmful to the body.  A good example  is  the
ability of  some enzymes in the liver to isolate and remove certain
heavy metals.  Unfortunately, the liver's intricate system is neither
perfect nor fool-proof; some toxics are not deactivated by the liver,
and some are even rendered more toxic by the liver.

     After passing through the liver, the blood enters general circula-
tion - going to all parts of the body.  It  is at this stage that the
most widespread damage is possible, as chemicals travel through  the
bones, nerves, glands, fat, muscle, and other tissues.  As previously
mentioned the toxics will tend to accumulate in areas depending on their
specific chemical properties.  Ultimately, the blood passes through the
                                  15

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kidneys and here many toxics which have not been absorbed by other
tissues are removed from the blood.  The kidneys are not perfect, they
cannot remove al1  toxic substances, and, of course, since the kidneys
remove the toxics they tend to be  exposed to the highest concentra-
tions.  This can lead to problems with the kidneys themselves, or other
parts of the urinary system.

      Ingestion of toxics may result from various kinds of exposure.  The
toxic substances may be in the food we eat, water we drink, or even  in
the air we breathe.  (The mucous which protects the lungs by trapping
and holding many Inhaled particles is gradually moved up the wind-pipe
and is swallowed.  Thus many of the toxics in the air will find  their
way into the digestive tract by riding on dust particles.)  The  body is
equipped to handle many of these substances, but many more are not
stopped and enter the blood system, thereby gaining access to the entire
body.

"The Air, the Air is Everywhere"*

(*from the song Pollution  in the Musical "Hair".)

      It is often easy to forget that air even exists.  Breathing  is
almost like the heartbeat:  a constant fact of life which we are  rarely
even aware of.

     There are well over two hundred million people in the USA today,
and every one of them is eating and breathing.  We have some degree  of
control over the food we eat, if we object to butter for one reason  or
another, we can buy margarine.  For breathing, however, there is  no
'substitute1 produce - the air we  have is the air we must breathe.

     As we breathe, air enters through the nose, passes through  the
nasal cavities, on  into the windpipe, and finally deep into the  passage-
ways of the lungs.  At each point  along the way there are  'filters'  to
help  to keep out dust and  particles.  The nose hairs trap  the largest
airborne particles  - frequently causing a tickling sensation which
causes us to "back-flush"  the system - to sneeze.  Particles which are
small enough to get by the hair without triggering a sneeze may  be
trapped in the mucous which lines  the sinuses and windpipe.  This mucous
moves constantly toward the esophagus (gullet) and is unconciously
swallowed.  (Interesting to note here that by this system  some airborne
toxics may become  Ingested toxics.)  Particles which are not stopped by
the mucuous layers  pass deeper  into the lungs.  This is where some big
trouble can start.   In order to better understand  the problem, however,
it  is best to side-track to explain some  things about how  lungs  work.

      The job that  the lungs must perform  - 21) hours a day  -  is to allow
oxygen to dissolve  from the air  Into the  blood, and to let C02 dissolve
from  the blood  into the air.  This is done by bringing the air and the
blood  into close contact,  in tiny  sacks in the  lung called aveoli.   It
is  important to note that  the aveoli do not expand and contract  with
each  breath - they  merely  open onto passageways  in which  the air is
moving. A  (surprizingly) good analogy may be made  by comparing the air-
aveoli relationship to the postal  service-residence relationship:  The
postman goes by every residence every day  (almost) and each trip he
                                  16

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accepts a little mail and leaves a little mail  - but he never drives
through the living room.  It's the same with the aveioli.  The air flows
by, not through, and with each cycle something  goes out and something
comes in.  The 02 and C02 drift in and out of the aveoli, but unfor-
tunately there is sometimes a little junk mail  - an occasional letter
bomb.

     The danger lies in that there is a range of sizes of particles
which are small enough to get past all of the filters, and yet too big
to drift in and out of most aveoli without making contact and sticking
to the aveolar wall.  The problem is made more complex by the fact that
very small  particles, such as individual molecules of some volatile
toxic substances, may pass across the membrane which allows the 02/C02
exchange between air and blood, thus entering the bloodstream directly
(note that in this case the blood does not go directly through the
liver, and so there  is reduced opportunity for that organ to remove or
deactivate toxics).  It is also possible that the particles may adhere
to molecules of airborne toxics, and thus transfer the toxics more
efficiently to the lungs.  This is apparently the situation with asbes-
tos workers who smoke cigarettes - the asbestos particles cause asbestos!
and cigarettes cause lung cancer,  but both together cause the odds of
getting lung cancer  to increase greatly. The theory is that the cancer-
causing substances adhere to the asbestos particles and are transferred
to the lungs more effectively because they are not exhaled, but settle
in the lungs along with the asbestos fiber. This is a grim example of
synergism - when two forces combine to become more powerful than they
would be if each acted alone.
                                  17

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                                ECOLOGY

              Ecology:  Toxics Moving  in the Environment
     Life means recycling.  Everything that  is, or was, or could be a
part of any living thing  is part of a grand  recycling scheme.  This
includes the air we breathe, the ground we walk on, the water we drink,
and our body i tself.

     The entire recycling process of nature  can be broken down into two
broad categories of events; growth, and decomposition.  Growth is char-
acterized by substances being brought together from less concentrated
sources -such as the bringing together of parts of the soil, air and
water for the new leaves of Spring.  Decomposition is just the opposite;
substances move from a concentrated, organized form into a disorganized,
more disperse form, such as the decay and 'disappearance* of the leaves
each Autumn.  As toxic substances enter the  environment, they also
undergo these same interactions of  increase  and decrease in concentra-
tion.  Perhaps the best way to explain this  is with an example or two.

     DOT, or dichloro-Diphenyl-Trichloroethane was widely used in the
U.S. as an insecticide.   tt was known to be  toxic to many insects, both
beneficial and harmful, but its effects on other forms of life were
largely unknown.  DDT has been very useful in the protection of many
crop plants, and has been used to fight Malaria in many parts of the
world.  After many years of use, however, it was found that DDT did not
decompose into simpler compounds, but moved  through nature's recycling
process virtually unchanged. DDT is an oily  substance (non-polar), and
therefore it tends to become concentrated in oily areas, such as fat
tissues and river-bottom muck.  It was later found that DDT is held and
accumulated in the fat tissues in animals - when the animal eats plants
or other animals with low concentrations of  DDT, nearly all of the DDT
is absorbed along with the good stuff, but DDT cannot be used or ex-
creted by the body, and so the animal accumulates DDT in fat tissues.
The DDT is relatively harmless as long as it remains trapped in the fat
tissue.  Problems arise, however, when the body is under stress, and
fats are used to provide emergency energy.  As the fats are used, the
DDT is released tnto the bloodstream.  The suddenly elevated concentra-
tions moves the DDT to all areas of the body in heavy dose, and may
cause trouble.   Birds.of prey, which accumulate very high concentrations
of DDT through their position at the top of  the 'Food Chain', are par-
ticularly susceptable to DDT poisoning.  The DDT seems to interfere with
the formation of the egg shell, resulting in thin shells which are
easily broken (even by the extraordinarily gentle parents as they incu-
bate the egg).   The production of eggs is a  time of great stress for the
female, so it Is probable that her fat reserves are being released,  DDT
and all, In an effort to cope with the stress.  It is ironic that DOT
should be held in relatively harmless form in the fat only to be re-
leased when ft has Its most detrimental effects.

     Iodine - 131  ('131 ) 's another toxic substance which may be
concentrated by the body,  fodine-131 is produced in nuclear fission
(splitting of Uranium and/or Plutonium in either bombs or nuclear power
plants). Iodine of ail  isotopes is absorbed by the body from food,  and


                                 18

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tends to accumulate in the Thyroid gland, where it is used in the
functioning of that gland.  This small  gland in the neck produces
hormones which affect nearly everything happening in the body.  If the
radioactive Iodine is ingested, it will naturally become concentrated in
the Thyroid gland.  As the Iodine decays, it gives off certain high
energy particles, which may cause unusual things to happen - events
which may lead to cancer of the Thyroid.  Fortunately, lodine-131 decays
fairly rapidly - half of it decays every 8 days - but it is continuously
produced in power plants and other nuclear sources.

     In conclusion, as long as each of us is alive and must maintain
ourselves and our children by eating food grown on the earth, and
breathing the air of the earth, we must  limit ourselves to using only
chemicals which are not toxic to ourselves or other species with which
we share the earth.
                                  19

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                             RISK ANALYSIS

                      Risk and Scientific Testing


     Science is estimation.  From the astronomers who estimate the
number of stars in the galaxy, to the zoologists who estimate how long
the average Gazelle lives, the work of a scientist is primarily forming
'educated guesses' based on a few observations.  One very important
thing that a scientist must do, is to estimate how far off the true mark
the estimate is likely to be.  For this reason scientific results are
customarily computed with a "confidence interval" - meaning a range of
values which is judged to have a high probability of including the
correct answer.   (We could KNOW the correct answer, if we could collect
all data from al1  possible situations, but that is impractical if not
impossible.)

     For example;  if a chemical is tested for carcinogenic!ty, it may be
mixed with the food or air of, say, 100 white mice.  Meanwhile, another
100 white mice are given the same food and air without the suspected
carcinogen.  After some period of time the mice are examined for cancer.
Assume that the results are:

                                 jt of cancers  in 100 mice

     Mice with chemical (test group)         6

     Mice without chemical (control group)   5
     What does this mean?  Five mice got cancer even without the chem-
ical, but one additional mouse got cancer with the chemical.  Would this
mouse have gotten cancer anyway?  Or was the cancer caused by the chemical
In other words, how much confidence can we have that the one extra
cancer was caused by the exposure to the chemical?  There are several
ways to decide this question.

     One could use 100,000 mice, and if there were 5,000 cancers in the
control  group and 6,000 In the test group, we would have to say that it
is overwhelmingly likely (though not technically proven) that the chem-
ical was causing the extra \% cancer rate.  But it is very expensive to
maintain 100,000 mice, and to pay the staff to run such a large test.
The alternative Is to Increase the dose of the suspected chemical.  Lets
say that we give 100 test mice ten times the former dosage - which they
would never be exposed to under "normal" conditions.  This time the
results are:

                                 # of cancers in 100 mice

     Mice with lOx chemical  (test group)     15
     Mice without chemical (control group)    5
                                  20

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 We  will  probably  agree  that  it  is  unlikely  that  all  15 in  the test group
 would  have  gotten cancer  without  the  chemicals  - but  it  seems that about
 5 mice per  100  get cancer with  or  without  the  chemical,  so we cannot
 blame  all  15  cancers  on  the  carcinogen!city  of  the  suspected  chemical.
 One mouse got cancer  from the chemical  when  the  dosage was one unit, and
 the cancer  rate increased to 10 per  100 when the concentration was
 artificially  increased  to 10 times  the  former  concentration.
         Dose  (say  ppm)

                1
               10
     Response  (increase  In  cancer  rate)
                     n
                    lot
Great.  Now we may say that each unit  (ppm) of
increase in cancer rate.   But we really cannot
do not know any of the points in-between - and
figure of U - it is
of -since it ts such a small change.
response1 curve through these points,
bi1i t ies:
                                                the  chemical  causes  a  13;
                                                be sure of  that  since  we
                                                what  about  that  first
                     not a  figure  that we  can  really  be  very 'confident1
                                      We  could  draw  almost
                                      for example  here  are
                             any  'dose-
                             three possi-
                                                     10
                                                      0:
                                             10
     GRAPH A
GRAPH B
                                                       GRAPH C
The 'x's in the above graphs represent the results that we got in our
Imaginary experiment (note that the 's' at zero does and zero response
has been added - ft Is a reasonable and necessary assumption that no
dose causes no increase).  Which one of these graphs looks most likely
to you?
                                  21

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     Right off the bat Graph B looks like a sham.  Why should odd doses
give higher rates than even doses?  That doesn't make sense.  Graph C
seems a bit less likely than A, but not quite as silly as B.  The best
thing to do at this stage is to get more data - and acknowledge that
there is at least a possibility of danger in exposure to this chemical
at any level.   (Note that Graphs A and C are like the Cigarette Smoking
example which was used in the introduction.  Graph A represents the type
of situation with Cigarettes and lung cancer, Graph C represents cigar-
ette smoking and cancer of the esophagus.)

     But this all brings us back to the question, "How much confidence
can we have that these results are accurate?"  If the one extra cancer
in the first experiment was just by chance, then the lower  'x' should be
at zero, and Graph C would look like the more correct graph.  If the
test group had been 100,000 mice,  the extra ]% cancer rate would be
represented by an additional 1,000 cancers, and  it would be hard to say
that it happened because of random chance, and so the 'x1 would be a
good 'x1; that is, we would have more confidence that it should be where
it is. Thus you can see that there is a trade-off here - the more mice
we use, the more confidence we have that our results are accurate, the
less mice we use, the  less confidence we can have in the results.

     This immediately brings up another trade-off:  Money.  How many
dollars will we spend for a given degree of confidence?  How about
switching to bacteria?  Bacteria can be raised by the billions, so we
can be very sure of the results - but the results are still on bacteria,
not man (or even mice).  It seems less likely that chemicals should
effect man and bacteria in the same way (although results indicate that
about 90% of the chemicals which cause mutation  in bacteria also cause
cancer in higher animals).  Another problem with bacteria is that they
have no higher organ system and so toxins such as nerve  toxins may not
be detected.

     As you can see, there are many problems associated with scientific
testing, and In the ultimate analysis the tests do not tell us anything
about what is or is not true in any absolute sense.  They do, however,
give us a narrow glimpse:  We must use our judgment to determine the
wider meaning of the data.  This judgment often  requires very personal
priorities to be weighed, and so it is not optimal to have only a very
few people with technical backgrounds making these decisions of judgment
for all of society.  This Is somewhat like the story of  the three blind
men who touch an elephant, one touches a  leg, one a tusk, and one the
long trunk - and they argue about it forever.  But people are not blind,
they are able to see both the beautiful gifts and the hidden terrors of
the chemicals which we are capable of producing.  Hopefully, we will be
able to tell the difference between the ones that are beneficial and
docile, like horses, and the ones which,  like the wild zebra, can be
captured but nevsr tamed and should be left unexploited  by  the human
race.
                                  22

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                   LAWS  DEALING WITH TOXIC  SUBSTANCES


 Laws

      A  series of  federal  laws were created during  the  1960's  and  1970's
 to  ameliorate the effects of pollution on  land,  in  the air  and  in  fresh
 and salt water.   They also deal with  the problems of  identifying,  con-
 trolling and removing hazardous substances,  in certain circumstances.
 Most  laws  have attacked  the problems  in piecemeal  fashion,  focusing on a
 few sources such  as  factory emissions without recognizing  the inter-
 relationship between air quality and water quality  outside  the  plant as
 well  as the safety of the working environment inside  the plant.   However,
 these laws are the tools which can be used to reduce  the dangers which
 the spread of toxic  substances poses  to the  quality of the  environment
 and human  health.  Each  law has certain strengths and weaknesses.

 Regulations

      Regulations  to  Implement the federal  laws are  developed  by the
 responsible administrative agencies, primarily the  U.S. Environmental
 Protection Agency.  The Occupational Safety  and Health Administration,
 Food  and Drug Administration, and Consumer Product  Safety Commission
 regulate employee  and consumer exposure as well.  Regulations spell out
 in  exact language  which pollutants can be controlled, which are labeled
 hazardous or toxic and what actions are required by the states.  They
 are published in  the Federal Register.

 Legal Definition  of  Toxic Substances

      Legally toxic substances are materials  which pose "unreasonable risk
 of  injury or hazard  to health or the environment."  'A more  comprehensive
 definition is found  in the New Jersey Water  Pollution Control Act  (P.L.
 1977, Chapter 7*0.  Sec. 3- r. "Toxic pollutant means those pollutants,
 or  combinations of pollutants, including disease causing agents, which
 after discharge and upon exposure, ingestion, inhalation, or  assimilation
 into any organism, either directly or indirectly by ingestion through food
 chains, will, on  the basis of information available to the commissioner,
 cause death,  disease, behavioral abnormalities,  cancer, genetic mutations,
 physiological malfunction, including malfunctions In reproduction, or
 physical deformation, in such organisms or their offspring."

 Laws

     At lease fifteen major federal  laws have been passed since the 1961
Oil  Pollution Act  to define which  substances  will  be designated toxic or
hazardous  substances and how they  are to be controlled.
                                    23

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 MAJOR LAWS  CONTROLLING  TOXIC  SUBSTANCES

 Lifted  in  toto  from  Toxic  Substances  Sourcebook  (w/minor  changes)
 Steven  S.  Ross,  Editor,  Environment  Information  Center,  Inc.,  New  York,
 New  York  (March  1978),  p.  15.

 EPA

 Toxic Substances  Control Act  of  1976:  places heavy  reporting  burden on
      industry;  EPA can  demand premarket  testing  of some existing and all
      new chemicals.

 Safe  Drinking Water  Act  of  1975:  carcinogens and toxic substances  in
      public drinking water  supplies.

 Resource Conservation and  Recovery Act of  1976:  disposal of toxic  and
      other  hazardous wastes in landfills;  requires identification of
      hazardous wastes and  permits for generators, transporters, and
      operators of treatment or storage facilities handling solid wastes.

 Water Pollution Control  Amendments of 1972 and 1977:  discharges of
      hazardous effluents into nation's waterways; clean-up of  hazardous
      spi.lls on  land  and  in  the water; control of discharges landward
    .of the three-mile  limit.

 Marine Protection, Research and Sanctuaries Act of 1972:  ocean dumping
      from three to twelve miles controlled by permits.

 Clean Air Act Amendments of 1970:  allows EPA to set national  emission
      standards for hazardous air pollutants;  standards now exist for
      beryllium,  asbestos, mercury, and vinyl  chloride.

 Federal Insecticide,  Fungicide and Rodenticide Act of 1972:  covers
      sales and use of economic poisons,  and foodstuff treated  with such
     poisons; counterpart legislation exists  for enforcement by USDA
     and FDA.

 FDA

 Federal Food, Drug and Cosmetic Act of 1906,  amended in 1938 and 1962:
     bars any detectable amounts  of carcinogens in foods and cosmetics;
     hair dyes specifically exempted.
Occupational Safety and Health Administration
Occupational Safety and Health Act of 1970:  hazardous materials in
     the workplace, or in products bought for use in the workplace.
Consumer Product Safety Commission
Consumer Product Safety Act of 1972:   commission to enforce earlier
     statutes;  excludes tobacco,  foods,  drugs,  cosmetics.

Federal  Hazardous Substances Act  of 1927,  amended 1976:   flammable,
     corrosive, allergenic or toxic materials in consumer  products.

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Flammable Fabrics Act of 1353 as amended:   clothing as well  as fabrics
     used for other purposes in the home.

Poison Prevention Packaging:  child-proof  caps on containers of chemicals
     drugs used in the home.

DOT

Oil Pollution Act of 1961:   oil spills, chemical  spills from ships.

Dangerous Cargo Act:  Tank Vessel Act:  Ports and Waterways  Safety Act of
     1972:  Pipeline Safety Act:  various  railroad and truck transpor-
     tation safety laws.
                                  25

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Bibliography for Toxic Substances

GENERAL REFERENCES

Audubon Magazine, includes articles on environmental pollutants.

Calabrese, Edward J.  Pollutants and High Risk Groups.  The Biological
     Basis of Increases in Human Susceptibility to Environmental and
     Occupational Pollutants.  Wiley-Interscience, 1978.

Center for Science  in the Public Interest.  The Household Pollutants
     Guide.  Anchor Books, 1978.

Consumer Reports, includes articles on toxic materials  in consumer
     products.

Consumer Research Magazine

Coulston, Frederick and F. Kerke Eds., Environmental Quality and Safety.
     Vol. 5 of Global Aspects of Chemistry, Toxicology and Technology as
     Applied to the Environment.  Academic Press, 1976.

Council on Environmental Quality,  Reports on Environmental Quality
     Washington, D. C. 1969 and on.  Annual report of  the Council on
     Environmental Quality.

Dinman, B.D., Non-concept of No-Threshold:  Chemicals  in the Environment.
     Science 175= 495-97-

Environment magazine, popular accounts of environmental problems.

Environmental Science and Technology

Fuller, John G., The Poison That Fell From The Sky.  Random House.
     New York, 1977.  Popular account of  industrial accident in  Italy.

Gardener and Cook,  Chemical Synonyms and  Trade Names,  7th Edition
     CRC Press,  1971-

Gosselin, Robert E. et al. Clinical Toxicology of Commercial Products.
     4th Edition, Williams and Wilktns,  1976.

Prevention, popularly written accounts of health effects of substances.

Sax, N.  Irving,  Dangerous Properties of  Industrial Materials, 4th Ed.
     Van Nostrand Reinhold Co. New York,  1975-

Science, weekly magazine  includes  reports of original  scientific work
     and articles on matters of  science  related  to economics and politics
     Series on Toxic Substances:  Toxic  Substances Legislation:  How
     Well Are Laws  Being  Implemented?  Science Volume  201:  1198. Sept.
     29,  1978.
     Chemical Carcinogens:  How  Dangerous are Low Doses?  Science Volume
     202:  37, Oct.  6,  1978.
                                  26

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BACKGROUND MATERIAL:   BIOLOGY,  ECOLOGY, PHYSIOLOGY, TOXICOLOGY, TESTING

Ariens, E.J., A.M. Simonis, and J. Offermeier,
     Introduction to General Toxicology, Academic Press, N.Y.  1976
     Discussion of cellular mechanisms, exposure, defense mechanisms,
     interaction of substances, metabolism of toxic substances.

Bell, George H., Textbook of Physiology and Biochemistry.  9th Ed.
     Churchill Livingstone, Medical Division of Longman  Inc. 1976
     Longman, Inc. 19 W. M»th St., N.Y.C. 10036, $25-  Well written
     textbook for undergraduate and postgraduate students.

Berry, James W. et al, Chemical Villains, A Biology of Pollution.
     C.B. Mosby Co., St. Louis, 1971* $9-95.  Basic background  information
     on ecology, biology and the effects and sources of  familiar  toxic
     materials.

Casarett, Louis J. and John Doul1, Eds.  Toxicology, the Basic Science of
     Poisons.  MacMlllan Publishing Co.  New York,  1975-  A graduate
      level text on toxicology.

Cole,  G.A.,  Limnology, C.V. Mosby, St.  Louis,  1975
     Test on  the  science of streams, lakes and  ponds.

Cudmore,  L.  Larison, The Center of Life: A Natural History of  the Cell.
      (Quadrangle Press, N.Y. Times, 1977  $8.95.   For  the  general  reader,
     well written  In a bright  style.

DeWitt, William,  Biology of the Cell:  An Evolutionary  Approach.
      W.B. Saunders,  1977,  $13-95-  Basic test  on biology.

Hunter, W.J.  and  J.G. Smeets,  Eds.  The Evaluation of  Toxicological  Data
      for  the Protection of Public Health.
      Oxford,  Pergamon Press,  1977-

Odum,  Eugene,  Fundamentals of  Ecology, W.  B.  Saunders  1971
      The  classic  test on ecology.

Pachter,  H.M.   Paracelsus: Magic into Science, Collier  Books, N.Y l°6l.
      Paracelsus (H93-15M)  is considered  the founder  of toxicology.  He
      promoted the concept  of  the  toxic agent  as a  chemical  entity and
      articulated  the dose/response concept.

Paget, G. E. Ed.   Methods  in  Toxicology.  F.A.  Davis Co.,  Philadelphia
      Blackwell  Scientific  Publications 1970.   Explanation  of early
      approaches to toxicology including LD  .

 Rothwell, Norman V.  Human  Genetics,  Prentice-Hall, 1977, $1^.50
      Accurate,  up-to-date, for college students, non-science majors.

 Tardiff,  Robert G.  tn  VJtro Methods  of Toxic Evaluation.   Ann.  Rev.
      Pharmacology and Toxicology 18:357'67  1978.
                                   27

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Waldbott, George, Health Effects of Environmental Pollutants, 2nd Ed.
     C.V. Mosby, 1979, $13.50.  Description of how various chemical
     pollutants can affect the human body.  Non-technical style with
     case histories, college level.

CHEMICAL CARCINOGENS AND MUTAGENS

American Cancer Society, Cancer Facts and Figures

Ames, Bruce, et al., Carcinogens are Mutagens : A Simple Test System
     Combining Liver Homogenates for Activation and Bacterial for
     Detection. Proc. Nat. Academy of Sciences 70: 2281-2285, 1973-

Auerbach, Charlotte, Mutation Research.  Problems, Results and Per-
     spectives, Halsted Press, 1976.

Busch, Harris, Ed. The Molecular Biology of Cancer, Academic Press,
     New York,
Council on Environmental Quality:  Carcinogens  in  the Environment.
     Reprint from the 6th Annual Report, Dec.  1975.  Available  from
     Supt. of Documents, U.S. Govt. Printing Office, Washington,  D.C.
     20*»02, $.75, Stock No. OM -01 1-00030-1 .

Epstein, S.S., Environmental Determinants of Human  Cancer,
     Cancer Research 3^:2^25,
Epstein, S.S., The Political and  Economic  Basis of  Cancer,
     Technology  Review, 78:1,  1976.

Fraumeni, Joseph F.  Ed.,  Persons  at  High Risk of  Cancer.  An  approach
     to  Cancer Etiology and  Control.   Proceedings of  a  Conference,  Key
     Biscayne, 197^.  Academic  Press,  London, 1975.

Hiatt, Watson and Winsten,  Eds.   Origins of  Human Cancer.   Cold  Spring
     Harbor  Conferences on  Cell Proliferation, k  Vols.  Cold Spring
     Harbor  Laboratories,  1977-

Hollaender,  Alexander, Ed.   Chemical Mutagens - Principles  and Methods
     for their Detection.   Plenum Press, New York,  k  VoTs.  1971  -  1975-

 I ARC:  Evaluation of Carcinogenic Risk of  Chemicals  to  Man. Vols 1-16.

Kraybill, H.F.,  and  M.A. ,  Mehlman Eds.,  Environmental  Cancer, Advances
      in  Modern Toxicology,  Vol.  Ill, Halsted Press,  1977.

National Academy of  Sciences Magazine, Summer  1978.

Saffiotti,  U. and Wagoner J.K.  Eds.  Occupational  Carcinogenesi s ,  Annals
     of  N.Y. Academy of  Science Vo.  271,  1976.
                                   28

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PESTICIDES:  INSECTICIDES, HERBICIDES, FUNGICIDES

Audus, L.J. Ed., Herbicides: Physiology, Biochemistry, Ecology, 2nd Ed.
     Academic Press, London/New York, 1976, 2 volumes.

Gunn, D.L. and J.G.R. Stevens, Eds., Pesticides and Human Welfare.
     Oxford University Press, 1976, $A paper.

Haque, Rizwanul and V.H. Freed, Environmental Dynamics of Pesticides.
     Vol. 6 in Environmental Science Research, Plenum, N.Y., 1975.

Hayes, Wayland J., Toxicology of Pesticides.  Williams and Workings Co.
     1977-

Pesticides Monitoring Journal.  Federal Working Group on Pest Manage-
     ment.  Group responsible to the Council on Environmental Quality.

Plimmer, Jack R. et al.  Editors, Pesticide Chemistry in the Twentieth
     Century.  American Chemical Society,  1977-  Review papers, dis-
     cussions of recognition of risks, resistance to pesticides.

U.S.E.P.A.  Pesticide Safety Tips  (A107)

U.S.E.P.A.  Safe Pesticide Use Around the  Home, Washington,  D.C.
     Sept.
Upholt, W., Pest Control Technology and  the  E.P.A.:  What  is Responsible
     Regulations?  Environmental Management, Vol.  1 pp. 484-^89,  1978.

Watson, David L. and A.W. Brown, Editors, Pesticide Management and
     Insecticide Resistance.  Academic Press,  1977  (1978?).
AIR POLLUTION

Aharonson,  E.F. et al., Editors. Air Pollution and  the  Lung.  Wiley,
     New York,  1976.

American Lung Association:  Air Pollution Primer.

Conservation Foundation:  Citizen's Guide to  Clean  Air.  A Manual  for
     Citizen Action.  Washington,  D. C.

Cote, W.A.  et al.  A Study of  Indoor Air Quality.   E.P.A. Research,
     Triangle Park, N. Carolina, Sept.  197*».

Finkel, A.  J. and W.C. Duel, Editors,  Clinical  Implications of  Air
     Pollution  Research.  Proceedings  of A.M.A. Air Pollution Medical
     Research Conference, Dec. 5~6,  197*».   Publishing Sciences  Group,
     Inc.   Acton, Mass. 1976.

Friedlander, Smoke, Dust and Haze, Wiley, 1977-

Good, W.O.  et al.  Sputum Cytology Among Frequent Users of Pressurized
     Spray  Cans.  Cancer Research  35:  316-21.  1975.
                                  29

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Hogan, Barbara, Aerosol Sprays.  Center for Science in the Public
     Interest. 1976.

Mansfield, T.A. Ed., Effects of Air Pollutants on Plants.  Society for
     Experimental Biology Seminar Series. 1976, Cambridge Univ. Press.

Mitre Corp. Scoring of Organic Air Pollutants:  Chemistry, Production
     and Toxicity of Selected Synthetic Organic Chemicals.  McLean, Va.
     Sept. 1976.

National Academy of Sciences, Committee on Medical and Biological
     Effects of Environmental Pollutants:  Ozone and other Photochemical
     Oxidants.  Washington, D.C. 1977.

National Academy of Sciences.  Physiological and Toxicological Aspects
     of Combustion Products.

Stern, Arthur C. Editor:  Air Pollution, 3rd Edition. 5 Volumes.
     1976 Vol  I    Air Pollutants, Their Transformation and Transport.
     1977 Vol  II   The Effects of Air Pollution
     1976 Vol  III  Measuring, Monitoring & Surveillance of Air Poll.
     1977 Vol  IV   Engineering Control of Air Pollution
     1977 Vol V    Management

U.S. Environmental Protection Agency.  Air Quality Criteria for Lead.
     Dec. 1977 E.P.A. 600/8-77-017-

Wade, W.A. et al.  A Study of  Indoor Air Quality. Journal of  the Air
     Pollution Control Assoc.  Sept. 1975, pp. 933'39-
ECONOMIC ANO LEGAL ASPECTS:

Ayres, Robert U. Resources, Environment and Economics.
     Applications of the Materials/Energy Balance Principle. Wiley-
      Intersclence, 1978.

Chemical Week.  McGraw Hill,  1221 Ave. of the Americas, N.Y.C. 10020
     Weekly magazine for Industry news from business viewpoint.

Chemical and Engineering News.
     Magazine for technical information related to economics of  the
     chemical industry.

Commoner,  Barry.  The Closing Circle, Nature, Man and Technology.
      1971, Alfred A. Knopf, Inc.  1972, Bantam Books Edition.

Down, C. G. and J. Stocks,  Environmental  Impact of Mining.  Halsted
     Press, 1977.

Dales, J.H.  Pollution, Property and  Price.  University of  Toronto
     Press,Toronto, Canada, 1972.
                                  30

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Ecology Law Quarterly, Special  Issue:  Hazardous Substances in the
     Environment, Law and Policy.   Vol. 7, No. 2, 1978. Available from
     School of Law,  Boalt Hall, Univ. of California, Berkeley, Calif-
     ornia, 9^720, $5.

Industrial Wastes, Scranton Gillette Communications, Inc.
     k}k S. Wabash Ave.,  Chacago,  111., 60605- Magazine for industrial
     waste processing  industry.

Resources for the Future, (1755 Mass. Ave. N.W., Wash.  D.C., 20036)
     Current  Issues in U. S. Environmental Policy.  Johns Hopkins Univ.
     Press, $A.95, available from above address.
                                  31

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