EFFECTS OF CHEMICALS 279
evaluation must be by indirect means. A causal relationship
has been demonstrated to exist between urban air pollution
and lung cancer. Lung cancer mortality patterns differ in
various sections of the United States and Great Britain. It
has been clearly shown that increased mortality due to lung
cancer is related to increased urbanization. A survey in the
late 1950s found lung cancer rates in the United States to be
39 per one hundred thousand in rural areas and 52 per one
hundred thousand in urban areas. Similar data were gath-
ered in Great Britain and the added effect of smoking was
evaluated. The conclusion of significance of urban air pol-
lution is inescapable.
The first demonstration that environmental pollutants
can cause genetic damage came with the discovery that
high energy radiation induces mutations. Later, the devel-
opment of the nuclear industry focused increased attention
on the dangers of unwanted genetic change. Associated with
possible genetic damage in this industry was the danger of
radiation induced carcinoma. Accordingly, safeguards were
developed and limits were set on radiation levels. These
were functions of exposure time. Limits were changed peri-
odically in the light of fresh evidence. It is of interest to
note that changes were usually downward. Radiation from
X-Ray machines and fluoroscopes was treated in the same
way. A widely available hazard was the fluoroscope for fit-
ting of shoes. It is impossible to determine possible genetic
damage from this source but it was probably considerable.
Such installations have all but disappeared. Medical and
dental radiation sources are firmly regulated. There was sus-
picion that some chemicals might induce mutations but only
about thirty years ago was the mutagenic effect of mustard
gas on fruit flies shown. There is concern in some circles
that strongly mutagenic chemicals, their effects not yet rec-
ognized, may already be in wide use.
A mutation can be a chemical transformation of a single
gene or a rearrangement of a chromosome. The former, called
a gene or point mutation, can cause an alteration in function.
The latter may be microscopically visible and is known as
chromosome aberration. In studies of human subjects the
aforementioned changes are not always easily determined.
When genetic function of a cell is changed while repro-
ductive capacity is unaltered the genetic change is transmit-
ted to descendant cells. Mutations in germ cells are most
serious in long-term effects because changes are transmitted
to future generations.
Mutagenic effects are of many types. These range from
lethal effects to changes so slight as to remain unnoticed. It
is thought that many inherited diseases are based in muta-
genic effects. At this time there is no known way to ade-
quately evaluate long-term mutagenic effects. It is a cause
for serious concern for future generations. Genetic effects
over a long term are statistical rather than discrete. As natu-
ral selection has had its effect over a long period, so will
externally induced mutations make their effect felt over a
long period. Dominant mutations appear in the next genera-
tion while recessive mutations require contributions from
both parents. This characteristic may not appear for many
generations.Most mutations are harmful or neutral. Many mutants
which in the past would have produced death or lessened
fertility now remain. This is due to higher standards of health
care. The former equilibrium, in which old mutations disap-
peared about as rapidly as new mutants appeared, has been
upset in favor of new mutants. Natural selection does not
apply as strongly as before. It has been suggested that medi-
cal problems of the future will be more and more due to
genetic origin. One estimate places our present health burden
as being 25% of genetic nature.
If a mutation causes a gene to have a sterilizing or lethal
effect, only one generation is involved. Less severe effects,
however, may involve many generations. The less severe the
effect, the more people will be exposed. Mild mutational
effects, affecting many people, will have a greater public
health impact than one severe, or fatal, case. Unfortunately,
many of these milder effects may be difficult to detect.
Many chemical mutagens in the environment pose threats
which have not yet been adequately evaluated. Mammalians
test systems are available but extrapolation from smaller ani-
mals to man is indeed difficult and liable to error.
Trimethylphosphate, until recently, was added to gaso-
line for control of surface ignition and spark plug fouling.
This substance has been implicated in chromosome damage
in rats. The dosage in rats at which damage occurred was at
subtoxic level. However, extrapolation of dosage levels to
man is difficult and man’s exposure to the substance in the
environment is almost impossible to estimate.
Congenital malformations are those abnormalities which
can be recognized at birth or shortly thereafter. The study
of these abnormalities, which can cause serious disability
or death, is known as teratology. A broader definition can
include microscopial, biochemical, and functional abnor-
malities of prenatal origin. It is estimated that about 3%
of live births involve congenital malformations, but this is
only an estimate. Lack of adequate data at the national level
makes such figures rather rough and probably inaccurate.
Three categories of human teratogens have been identi-
fied. These are: (1) viral infections, (2) ionizing radiation,
and (3) chemicals. Thalidomide is the best known of the
third category. Experimental evidence of teratogenicity of
some compounds had been in existence for many years but
requirements of three generation reproductive tests in ani-
mals were established only after the sensational thalidomide
disaster of 1962. Some questions concerning the validity of
such tests have been raised.
Pollutant materials to which humans are exposed must
be examined for toxicity. These examinations must also
include specific tests for carcinogenicity, mutagenicity, and
teratogenicity. These effects have been studied in the past
by separate disciplines and there has been inadequate inter-
change of results and ideas. It is to be hoped that the emerg-
ing profession of environmental scientist will aid in breaking
down these historical and somewhat artifical barriers among
disciplines.
There is need for more sensitive and reliable methods
of testing effects of single chemicals, degradation products
and mixtures. External environmental effects must also beC005_004_r03.indd 279C005_004_r03.indd 279 11/18/2005 10:21:38 AM11/18/2005 10:21:38 AM