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Author

on 37
Anderson, John M.

Corporate Author
ROpOrt/ArtlClB Title

DDT:

Sublethal Effects on Brook Trout Nervous System

Journal/Book Title

science

Year

1969

Month/Day

A ril 25

Color

n

Number of Images

2

P

Alvin L. Young filed this item under the category
"DDT/Human Toxicology and Environmental Fate"

Wednesday, April 11, 2001

Page 1187 of 1242

�cent rabbit serum; pH 7.0; without
agar), with incubation for 24 hours at
37°C. The end point of activity was
complete inhibition of growth. After
isolation of metronidazole-resistant organisms, experiments were done in
hamsters to compare the efficacy of
metronida/ole against the metronidazole-sensitive and -resistant strains.
Hamsters were infected with 24-hour
cultures of vaginal washings from donor
animals infected with either the sensitive or the resistant strain of T. foetus.
After 1 week a vaginal smear was taken
to confirm infection. Groups of ten
animals each were then treated orally
with up to 200 mg of metronidazolc
per kilogram of body weight, daily for
four successive days. A group serving as
infection controls was treated with the
drug diluent, 0.5 percent gum tragacanth.
Twenty-four hours after each treatment, a vaginal washing was taken
and placed in Diamond's medium con, taining 100 units of penicillin G and
100 fig of streptomycin per milliliter.
The sample was then incubated for 24
hours at 37°C, examined, and scored
for trichomonads present. An additional sample was taken 1 week after the
last treatment. The degree of infection,
designated as the infection score, was .
determined by assigning a value of 0,
1, 2, or 3 to each culture examined,
0 indicating no detectable organisms
and 3 indicating more than 100 trichomonads per microscopic (X 10) field.
The isolate from the animals treated
with the aforesaid suboptimum doses of
metronidazole was 8 to 16 times more
resistant than the parent strain. The
minimum inhibitory concentration of
metronidazole for the parent strain
ranged from 0.0975 to 0.195 /xg/ml,
whereas that for organisms isolated
from the metronidazole-treated animals
ranged from 1.56 to 3.12 /tg/ml. There
was no further increase in resistance to
metronidazole in infected animals in
which treatment was continued for a
period of about 3 months.
After four oral treatments with
metronidazole, hamsters infected with
the metronidazole-sensitive strains of
T. foetus had a significant reduction in
parasites, even at 50 mg/kg per day
(Fig. 1). One week after the last treatment, an exacerbation of the infection
was observed. Animals infected with
the metronidazole-resistant strain of T.
foetus and treated with metronidazole,
even at 200 mg/kg daily for 4 days,
440

showed no change in parasite numbers
during the test period.
Resistance to antiprotozoal agents is
an important problem in animal and
human therapy. Although metronidazole-resistance apparently is not a widespread clinical problem (4), its presence may be more common than
believed. Most clinicians do not isolate
organisms and test for resistance in
cases of therapeutic failure. Furthermore, epidemiological problems cloud
the search for resistant organisms in
recurrent cases, as the long-term followup required is of little value if the
treated individual cannot be isolated
(5). Chloroquine-resistance in human

malaria first became evident after
the drug had been used for many
years. Similarly, metronidazole-resistance could prove to be a significant
clinical entity.
P. ACTOR, D. S. Ziv
J. F. PAGANO
Research and Development Division,
Smith Kline &amp; French Laboratories,
Philadelphia, Pennsylvania 19101
References
1. I. dcCarneri, Lancet 1966-1, 1042 (1966).
2. B. M. Ilonigberg, Proc, Int. Congr. Parasltol.
1st Rome, 1, 368 (1966).
3. I. deCarneri, ibid., p. 366.
4. L. Watt, Practitioner 195, 613 (1965).
5. S. C. Robinson and D. W. Johnston, Canad.
Med. Ass. ]. 85, 1094 (1961).
13 January 1969

•

DDT: Sublethal Effects on Brook Trout Nervous System
Abstract. When brook trout are exposed for 24 hours to sublethal doses of
DDT, the cold-blocking temperature for a simple reflex, which shows lability
related to thermal history, is altered in a way suggesting that DDT is affecting the
thermal acclimation mechanism. Sublethal dosage of DDT also prevents the establishment of a visual conditioned avoidance response.
Fish show behavioral changes after
exposure to sublethal concentrations
of pesticides (1, 2) that may act on
either peripheral or central (or both)
nervous structures. One receptor system (the lateral line) is markedly affected by sublethal concentrations of
DDT (3). Although there is little supporting evidence, the central nervous
system (CNS) nevertheless seems the
most likely site for the pesticide-sensitive region responsible for changes in
complex behavior.
Two different behavioral responses
of brook trout Salvelinus fontinalis to
sublethal exposure to DDT implicate
the CNS as the target site. The first is
represented by changes in the low temperature
(cold-block
temperature)
which is just sufficient to extinguish
the propeller tail reflex (4). The spinal
cord is the site for this cold blockage
(5). The second response involves visual conditioning of an avoidance response that is formed in the optic
tectum (6).
The fish ranged from 6 months to 2
years old. They were fed DDT-free
beef liver once daily. To minimize the
amount of detritus present, the fish
were not fed for 3 days prior to and
during the period of treatment. All
DDT exposures were for 24 hours and
were carried out in 6 liters of continuously-aerated water at the acclimation

temperature in glass jars, one fish per
jar (7). The DDT was always added
to the water in 0.3 ml of acetone. Control fish were treated the same as were
experimental ones, except that no DDT
was dissolved in the acetone. The fish
were tested in clean water, and, unless
otherwise specified, each experiment

9(0),

.£

4

3

° 2

I -

| 3(38 )

40

60

DDT concentration (ppb)

Fig. 1. The effect of acclimation temperature and exposure to DDT on the coldblock temperature of the propeller tail
reflex in the brook trout. The numbers
refer to the total number of fish tested
and (in parentheses) the percentage which
failed to block down to the lowest temperature obtainable, 1°C±S.E, also
shown. Solid line, fish acclimated at 9°C;
broken line, fish acclimated at 18°C.
SCIENCE, VOL. 164

�began immediately after the 24-hour
^sposure to DDT.
Cold-block temperature was determined as described (5), except that our
stimulus was a 10 msec train of square
wave pulses (1 msec and approximately
10 volts each at a rate of 400 per second).
As expected, for control fish acclimated at 18.0°C, the cold-block
temperature was significantly higher
than for the ones acclimated at 9.0°C
(Fig. 1). Treatment with DDT also
altered the cold-block temperature. The
response of DDT-treated fish acclimated
at 9.0°C was not quite the same as
that of those acclimated at 18.0°C
(Fig. 1). The difference, however, may
be more apparent than real. The lowest temperature obtainable with our
apparatus was l°C and not only did
many fish acclimated at 9 d C fail to
block, but also, for those fish that did
block, the blocking temperature was
about 1°C. If much lower temperatures had been possible, the response
of fish acclimated at 9°C might have
differed.
To say that DDT can alter the coldblock temperature just as can thermal
acclimation, may be more than a convenient analogy. Sublethal concentrations of DDT, like thermal acclimation, shift the selected temperature of
brook trout (and other salmonids) (2).
Low doses lower the selected temperature; higher doses raise it in a pattern
very similar to that shown in Fig. 1
for the cold-block temperatures of fish
acclimated at 18°C. The DDT may be
interfering somehow with the thermal
-acclimation mechanism. This would be
consistent with our hypothesis that
DDT acts upon central nervous structures because changes in selected temperature are thought to be controlled
by the CNS (8).
The effect of DDT on a nervous
function more complex than the propeller tail reflex was investigated by
exposing trout acclimated at 9°C to
20 parts per billion of DDT and then
comparing their ability to learn a simple
conditioned avoidance response with
the ability of untreated fish.
Brook trout have an individual preference for either the lighted or darkened side of a two-chambered aquarium. We trained our trout to avoid
the side of their preference. The nonpreferred lighting was the conditioning
stimulus; electric shock was the unconditioned stimulus. Fish were consid25 APRTL 1969

Table 1. The response of fish during the establishment of the conditioned avoidance response.
The "avoidance" response is the one used for the training criterion. The fish tested at various
.times after DDT exposure were all different fish and had not previously been tested.

Day

Pish
tested

(No.)

A e

Missest

Escapest

&lt;%)

( o)

13.0

S
(No.)

52.0

35.0

0.0
2.9
7.8

Avoidances§

(%)

Untreated

12

30.3

DDT-treated

1
4
7

6
6
6

&gt;25

94.0

6.0

&gt;28.3
&gt;29.5

52.0
43.0

45.1
49.2

* Trials per fish until trained to .avoid preferred side.
t Failures to leave the initially preferred
side of a two-chambered aquarium during the electric shock period. Misses typically occurred
early in the training session.
I Successful exit during the electric shock period.
§ Departure
after lighting change but before the electric shock.

ercd to be conditioned when they
showed eight consecutive proper avoidances. The apparatus and method of
training were similar to that used by
Roots and Prosser (5).
Although untreated naive fish took
only about 30 trials to become conditioned, not one of the DDT-treated
naive fish became conditioned (Table
1). Training was discontinued after approximately 25 trials because by this
time, after almost 6 minutes of intermittent electric shock, the fish had become refractory and were sitting on
the bottom, often at an angle, failing
to exhibit any overt response to the
shock. The duration of the DDT effect
was investigated by testing the response
of naive fish 4 and 7 days after DDT
exposure. These fish showed some improvement in performance. Fewer
misses and more escapes and avoidances were observed. However, the
improvement was at best slight, for it
did not appear that the fish would
ever show the required eight consecutive avoidances. Even after 7 days, no
fish showed even two consecutive
avoidances.
Evidently, DDT treatment reduces
the ability of fish to form an association between the connecting doorway and escape from shock. There
was no apparent impairment in either
the swimming or visual abilities of the
fish.
The effect of DDT treatment on the
retention of the conditioned avoidance
response was determined by comparing
the number of trials initially required
to attain full conditioning with the
number required for the same fish
when tested 24 hours later. Six fish
served as controls and six as experimcntals. The second performance of
control fish was enhanced by the previous training, the difference between
the initial 32.7 ± 3.04 (S.E.) trials and

the subsequent 11.2 ± 1.20. trials being
significant (P &lt; .005). The fish exposed
to DDT required 27.8 ± 1.80 trials
before treatment and 24.2 ± 1.80 trials
after treatment. The difference is not
significant (P &gt; 0.5). It is as if the
DDT treatment had converted the previously-trained fish into naive ones.
Yet, clearly something has been retained by these fish, for if they had not
had the training session prior to the
DDT exposure, then, as shown in
Table 1, they would not have been
able to learn at all.
JOHN M. ANDERSON*
MARGARET R. PETERSON!
Department of Biology,
Carleton University, Ottawa, Canada
References and Notes
1. D. M. Osilvie and J. M. Anderson, J. Fisheries
Res. Board Canada 22, 503 (1965); R. E.
Warner, K. K. Peterson, L. Bergman, /. Appl.
Ecol. 3 (Suppl.), 223 (1966); R. E. Warner,
World Health Organ. Butt. 36, 181 (1967);
L. F. Stickel, Report on the Unintended Occurrence of Pesticides in the Environment
Sponsored by O.E.C.D, and Development and
Natural Environment Council of the United
Kingdom (Patuxcnt Wildlife Research Center, Laurel, Maryland, 1967).
2. M. Y. Javaid, thesis, Carleton University,
Ottawa (1967).
3. J. M. Anderson, J. Fisheries Res. Board
Canada 25, 2677 (1968).
4. This reflex, first described by von Hoist,
[Z. Vergl. Physiol. 20, 582 (1934)], consists of
a weak propeller-like movement of the tail in
response to electric stimulation of the gular
region.
5. B. I. Roots and C. L. Prosser, /. Exp. Biol. 39,
617 (1962).
6. F. K. Sanders, ibid. 17, 416 (1940).
7. The DDT was a technical mixture consisting
of 80 percent 1, 1, l-trichloro-2,2-bis(p-chlorophenyl) ethane and 20 percent 1, 1, 1-trichloro2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane obtained from Fisher Scientific Company as
Reagent Grade.
8. K. C. Fisher, in Physiological Adaptation, C.
L. Prosser, Ed. (American Physiological Society, Washington, 1958), p. 3.
9. Supported by grants from Fisheries Research
Board of Canada and National Research
Council of Canada.
* Present address: Fisheries Research Board of
Canada Biological Station, St. Andrews, New
Brunswick,
t Present address: Department of Physiology and
Biophysics, University of Illinois, Urbana,
61801.
23 January 1969
441

�Circadian Rhythm of Serotonin in the Pineal Body of
Immunosympathectomized Immature Rats
Abstract. In the pineal body of the immature rat the circadian rhythm of
serotonin persists when sympathetic innervation is abolished by the administration
of nerve growth factor antiserum. This rhythm is regulated by a mechanism
that does not involve the sympathetic innervation and is, therefore, fundamentally
different from that in the adult.
In the past 10 years major advances
in our knowledge of pineal physiology
have been established. Compounds within the pineal body have been identified
and their levels measured. Many of
them have been shown to have a circadian rhythm that is dependent upon environmental lighting mediated through
the retina and the sympathetic nervous
system (7).
Serotonin is one of these compounds.
In the rat pineal it exists in high titers
(2) and has a circadian rhythm in
which levels are lowest 4 hours after
the onset of darkness and highest 6
to 8 hours after the onset of light (3).
Sympathetic postganglionic fibers from
the superior cervical ganglion (4) regulate the rhythm. After bilateral superior cervical ganglionectomy or severance of preganglionic fibers the cycling
of serotonin in the pineal body is
abolished (5, 6). Although this role of
the sympathetics has been confirmed in
the adult rat, the following observations
suggest that pineal serotonin may not
be regulated through sympathetic innervation in the immature animal.
As early as 6 days postpartum the
circadian rhythm of serotonin is present (7), but at this age there is a sparsity of intrapineal sympathetic nerve
fibers ( 8 ) . To learn the significance of

this apparently inadequate innervation
we undertook the study, described in
this report, of serotonin levels in totally
denervated pineals in young rats. Because of stress and mortality after superior cervical ganglionectomy, we chose
to den3rvate the pineal by immunosympathectomy (9).
Holtzman rats of both sexes were
given bovine nerve growth factor antiserum (NGFA) (10) within 6 hours
after birth and again 24 hours later.
Experimental and control animals were
maintained together in a controlled environment. The temperature was 19° ±
1°C, and fluorescent lights were kept
on from 5:00 a.m. to 7:00 p.m., that is,
a cycle of 14 hours of light and 10
hours of darkness.
Animals were decapitated at either
8 or 20 days of age—one group at 1:00
p.m. and another at 11:00 p.m. Pineals
were dissected quickly, weighed on
saline-moistened filter paper on a Roller Smith torsion balance, homogenized
in groups of two in 0.5 ml of 0.1 N HO
and 0.5 percent ascorbic acid, and
refrigerated. Within 24 hours serotonin
was assayed on a Farrand spectrofluorometer (model No. 104244B) according to the method of Quay (11). Since
fluorescence microscopy reveals the extent of sympathetic nerve suppression

Table 1. Serotonin levels in the pineals of normal and immunosympathcctomizcd young rats.
Each group contained 10 or 12 animals. There is no significant difference between pineal
weights of groups in each of the four treatment categories. N.S., not significant.
Treatment

Pineal
weight
(nig)

Serotonin
(ng/pineal)

Significance of difference
Groups

Level

Rats 8 days old
None
Day*
'Nightt
Night-lighted
NGFA (1100 unit
g-* day-1)

Day
Night
Night-lighted

0.470 ± 0.035
.502 ± .022
.410 ± .013

30.5 ± 2.20
13.3 ±1.60
23.1 ± 1.50

Day: night
Day:night-lighted
Night : night-lighted

.001

.473 ± .015
.527 ± .030
.483 ± .017

29.6 ± 1.63
10.0 ± 2.33
14.5 ± 2.78

Day:night
Day:night-lighted
Night: night-lighted

.001
.001
N.S.

.02
.01

Rats 20 days old
None

Day
Night
NGFA (600 unit
g-1 day-1)

Day
Night
* Day, 1:00 p.m.

442

0.586 ± 0.039
.632 ± .037

54.5 ± 4.59
13.5 + 4.12

Day: night

,001

.549 ± .031
.550 ± .034

61.0 ± 3.52
19.0 ± 1.81

Day: night

.001

t Night, 11 p.m.

(12), a sample of pineal bodies frojoj.
each group of treated animals was examined by this method. In addition,
stretch preparations of the iris of all
the 20-day-old animals used in the experiment were examined by fluorescence microscopy. In normal control
pineals (from animals 8 and 20 days
old), the sympathetic innervation was
present and similar to that described
elsewhere (8).
In animals injected with NGFA (600
unit/g) there was no nerve fluorescence
in the iris preparations, and although
denervation of the pineal was almost
complete, occasionally a few scattered
fibers remained. When the dosage was
increased to 1100 unit/g, pineal nerve
fluorescence was abolished.
Prolonging the light period into the
normal dark period prevents the nocturnal fall in pineal serotonin in both
adult and immature animals (6, 7). To
clarify the role of sympathetics in the
immature rat, it was important to determine whether prolonged lighting
would modify the amount of serotonin
in denervated pineals. Thus on the day
the animals were killed a third group
was given four additional hours of
lighting, that is lights remained on until
11:00 p.m., the time they were killed.
Results in Table 1 show that at both
8 and 20 days of age there is a circadian rhythm in rat pineal serotonin and
that after immunosympathectomy the
rhythm persists unchanged. Thus its
regulation must be through a mechanism fundamentally different from that
in the adult.
la the adult, central nervous system
stimuli that regulate serotonin levels
reach the pineal via sympathetic fibers
(5). Since rhythm persists in the young
animal after denervation, it seems reasonable to speculate that in the immature rat the rhythm is intrinsic to the
pineal itself. However, the origin and
nature of its regulator remains unknown. An endocrine influence in immature rats has not been studied, but
in the adult, removal of endocrine organs does not modify pineal serotonin
rhythm (6).
The results of Table 1 also show that
in sympathectomized animals additional
lighting did not elevate serotonin levels
above the nocturnal low. From the first
observation—that serotonin rhythm persists in the absence of sympathetics—
one might presume that innervation has
no regulatory function on serotonin
metabolism in the young rat. However,
since additional lighting prevents the
nocturnal fall in serotonin in intact
SCIENCE, VOL. 164

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                  <text>Alvin L. Young Collection on Agent Orange</text>
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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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                <text>Anderson, John M.</text>
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                <text>April 25 1969</text>
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                <text>DDT: Sublethal Effects on Brook Trout Nervous System</text>
              </elementText>
            </elementTextContainer>
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                <text>aquatic animals</text>
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                <text>health effects</text>
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                <text>pesticide toxicology</text>
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                <text>fish population</text>
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ones
Bababunmi, Enitan A.

Corporate Author
Report/Article TltlB Toxins and Carcinogens in the Environment: An
Observation in the Tropics

JOUmal/BoOk TltlO

Journal of Toxicology and Environmental Health

Year
Month/Day
Color

D

Number of Images

9

DOSCrlptOn NotOS

^'vin ^- Young filed this item under the category
"DDT/Human Toxicology and Environmental Fate"

Wednesday, April 11, 2001

Page 1188 of 1242

�TOXINS AND CARCINOGENS IN THE ENVIRONMENT:
AN OBSERVATION IN THE TROPICS

Department of Biochemistry, School of Medicine,
University of Ibadari, Ibadan, Nigeria

The incidence of primary liver cancer in the countries of tropical Africa is the highest in
the world. There, is a growing belief that the relatively high prevalence of hepatocellular
carcinoma in Niyeria may have a multiple chemical factor etiology in such forms as food
contaminants, herbal leas, and environmental chemicals. Major chemical toxins and
carcinogens that have been identified so far in the tropical environment include
supotoxin, cycasin, mushroom toxin, capsaicin, oxalic acid, prussic acid, fluotooleic acid,
N-nitroso compounds, aflatoxin, palmotoxin, pyrrolizidine alkaloids, quinine, DOT, and
eye/ornate.

INTRODUCTION
During the past two decades, there has been an increasing awareness of
the hazards to human and animal health from various chemical substances
Jthat occur in the tropical environment. There is evidence to indicate that
azarious health problems, including some forms of cancer, have their origin
in the presence of toxic chemicals in medicines, herbal residues, pesticides,
foods, and drinks. Some of these problems are common to countries
throughout the world, while others are peculiar to Africans who live in the
tropics. For example, altogether the incidence of primary liver cancer in
adult males is • the highest in the world in African countries such as
Nigeria, Uganda, and Mo/ambique (IARC, 1971).
The primary objective of the present review is to focus attention on
the presence of toxic chemicals in foods and in the environment of
tropical African countries, particularly Nigeria, which is the most populous
country in Africa. Some of these toxins have been shown to possess
carcinogenic (or mutagenic) properties in various biological systems.
However; in a large number of cases, adverse effects of some of these
toxic substances on human health are not known. It is hoped that this
paper will have the important effects of stimulating more research into the
special toxicological problems that arc of concern to people living in the
tropics.
This article was written during the author's tenure as an ICRCTT Fellow of UICC (1977) at
the Department of Biochemistry and King's College, University of Cambridge, Cambridge, [England.
Requests for reprints should he sent to fcnitan A. Bababunmi, Department of Biochemistry,
School'of Medicine, University of Ibadan, Ibadan, Nigeria.
691

journal oi Toxicology and Environmental Health, 4:691-699,1978
Copyright © 1978 by Hemisphere Publishing Corporation

0098-4108/78/040691-09$2.25

�692

E. A. BABABUNMI

ENDOGENOUS FOOD TOXINS
Endogenous food toxicily is widespread in tropical Africa. Nicholls ct
al. (1961) dealt with the various types.of tropical foods that carry toxins.
The review of Crampton and Charlcsworth (1975) adequately covers the
occurrence of food toxins in the nontropical world.
Hypoglycin
This toxin is contained in the unripe fruit of the food plant, Blighia
sapida. In Nigeria the fruit is called isin, whereas it is commonly known as
ak.ee in Jamaica. There are two types of this toxin, A and B. Although
both types are biologically active, the A type (/J-mcthylenecyclopropylalaninej is the more toxic. Very little work has been done on the chemistry
and the biological function of the B type.
Dioscorine
This toxic chemical is sometimes referred to simply as dioscorea toxin;
it is an alkaloid that is present in Dioscorea hispida. The main toxic
species of these tropical yams of West Africa are D. hispida, D.
dumctorum, D. sansibarensis, and D. bulbifem. Since the isolation and
identification of the related alkaloid dehydrodioscorine by Bevan and H.rst
(1958), scientists have not looked into the existence of these or other
structures in the other species of the wild yams.

Sapotoxin
Some tropical foodstuffs such as soybean, breadfruit, tomato, melon,
orange, and groundnut contain some sapotoxin, which, at high concentrations, has drastic effects on humans. The toxin can cause gastroenteritis
and produce paralysis of the nerve centers. Sapotoxin is a nitrogen-free
glycosidc.
Cycasin
Cycasin occurs in plants of the family Cycadaceae, which are indigenous to tropical and subtropical regions (IARC, 1972). The biologically
active moiety of cycasin is the aglycone melhyla/oxymelhanol. Cycad
seeds are used as medicine in some parts of Africa, Indochina, and India.
Feeding of a cycad diet has been shown to induce malignant tumors of
the liver in the rat, mouse, hamster, fish, and guinea pig (IARC, 1972).
Mushroom Toxin
A large number of mushroom species are edible, but certain species
that arc eaten in the tropics are poisonous. Examples of toxins elaborated
by these species are agaritine (Ayaric'us bisporus toxin) and champigeon
(A. hortemis toxin). Muscarine and Amanita phalloictes toxin have been
reported to be toxic by Nicholls el al. (1961).

�TOXINS AND CARCINOGENS IN THE TROPICS

693

Names for different species of mushrooms are descriptive in many
pails of I he tropics. In the western state of Nigeria, these names give an
indication either of the habitat, morphology, and texture or of the growth
habitat of the fungi (Oso, 1975). Corprinus ephemerus, a fungus that
grows on dunghills, appears at night or early in the morning, and within a
very short time the pilcus is fully expanded. However, it deliquesces in the
sun. It is considered poisonous by the Yoruba people of Nigeria, and local
doctors use it in the preparation of some (harms. (Extracts of the fungus
should be tested for mutagenicity.
Capsaicin (Red Pepper Toxin)

The substance is the active principle of the plants Capsicum annum
and C. frutescens. It is a powerful irritant and a skin blister. Although
these plants are rich in vitamin C, excessive feeding on them can be
dangerous. Species of pepper such as Piper nigrum contain alkaloids and
volatile oils that are toxic to both animals and humans.
Halogeton Toxin (Oxalic Acid)
Plant species such as Halogelon ylomeritus, Celosia argentae,
Amaranthus candatus, Celosia laxa, and Talinum are used as food in
tropical Africa, especially on the west coast. These vegetables contain
significant levels of oxalic acid (Oke, 1967). There are conflicting data on
the lethal dose for humans. However, Oke showed that an average healthy
Nigerian would consume about 6 g of oxalic acid daily, on the basis that
50 g of fresh vegetables could be consumed at a meal.
Cyanogen (Prussic Acid)

Tropical plants, cassava, mai/ie, and sugar cane are good sources of
cyanogenetic glycosides such as linamarin and dhurrin. Cassava (manioc;
Man/hot ulilissima} is the most widely grown of all tropical root crops. It
is mainly a carbohydrate food with a very low protein content. In West
Africa, manioc flour (gari). has become a major diet. In the West Indies the
dried flour is called farina. All over the tropics it is used as food for the
young and adults in one form or another.
The en/yme linasc liberates prussic acid (HCN) from linamarin. HCN is
toxic to many species of animals, including humans. The production of
HCN varies with the variety of the plant and the conditions of cultivation
(Osuntokun et a!., 1969).
Although significant amounts of HCN arc said to occur only in the
bitter variety of cassava, there is in fact no clear differentiation between
the sweet and hitler strains. The fact that the cortex of the root contains
the highest concentrations of the toxin provides biological protection for
the plant against invading insects. Chronic cyanide intoxication by laboratory animals has resulted in neural damage in the guinea pig, rabbit, sheep,
and cat.

�694

E. A. BABABUNMI

Fluoruoleic Acid
The seeds of the West African plant Dichapctalum toxicarum contain
fluoroeleic acid and some minute amounts of shorter-chained fluoro acids.
These fluoro compounds arc toxic.'Local, doctors in the countries of West:
Africa often administer the seed extracts in an attempt to produce loss of
motor activity, loss of sensation, and sometimes death (Peters el al.,
I960). Free oleic acid uncouples oxidative phosphorylation (Pressman and
Lardy, 1956).
/V-Nitroso Compounds
.Dimclhylnilrosaminc (DMN) and diethylnilrosamine (DEN) have been
detected in measurable quantities in several alcoholic beverages in Nigeria
(joaquim, 1973). Bababunmi et al. (1977) reviewed the extent of contamination of these drinks by the two carcinogens. There is some evidence
that the formation of these nil.rosamines involves bacterial action.

FUNGAL TOXIC CONTAMINANTS
Fungus-infected foodstuffs are the cause of many types of food
poisoning (see Kadis et al., 1972). In the tropics, a Variety of fungal
species have been reported to be involved in some toxicity syndromes.
Notable examples are Asperyi/lus, Penicil/ium, Stachybotrys, Trichoderma,
f-'usarium, Pseudomonas, and .Helminthosporiurn species. The most
ubiquitous in Nigeria are Aspergillus and Pcnicillium. Many strains of each
of these fungi are toxigenic. Among the common toxic metabolites of the
aspergilli arc aspergillic acid, flavacol, j3-nilropropionic acid, kojic acid,
sterigrnatocystin, ochratoxin, aspet toxin, aflaloxin, and palmotoxin.
Penicillium elaborates the mycotoxins patulin, islandiloxjn, lutcoskyrin,
rugulosin, cifrinin, frcquentic acid (citreomycctin), gliotoxin, costaclavine,
and citreviridin. Of these, aflatoxin has been studied most extensively,
mainly because of its potent carcinogenic properties. A comctabolile of
aflaloxin, palmotoxin, has been the subject of investigation for some years
in this laboratory. Many other naturally occurring toxins (Table 1) that
are known should be tested for carcinogenictty.
Aflatoxin
The literature on the biochemistry, toxicity, carcinogenicity, and
mutagenicity of aflatoxin is enormous (Goldblatt, 1969; Wogan, 1975a,
1975b; IRAC, 1976), The discovery of aflatoxin in the tropics (Asplin and
Carnagnan, 1961) as a contaminant of human and animal foodstuffs
(groundnuts) aroused the interest of scientists all over the world because
of i t . health ha/aids and possible economic effects on the producers of
these foods. Nigeria is one .of the world's major exporters of groundnuts.
Other tropical foods that arc vectors of aflatoxin are beans, corn, rice,
cocoa, and wheat.

�TOXINS AND CARCINQGtNS IN lilt. TROPICS

695

TABLE 1. Sonic Known Naturally Occurring Toxins

Toxic sulislance

Occurrence in

l-'usaric acid

Fiisariuni oxysp oiium

Pcriconin
T toxin
llclminthosporo'sidc
Tabtoxin
Javanicin

Pcriconia circ'inatu
1 lei min tli ospvrium may dis
Hvlniitithosporium sqcchari
Pseudomonus coronal aciens
f-'usarium solan!

Possible human
exposure through
Tomato, sorghum,
maize
Sorghum
Maize
Sugarcane
Tobacco
Maize

Aspergillus flavus, the main source of aflatoxin, is common in air and
soil, It will grow on agricultural products and food materials in a favorable
environment with a relative humidity of 70-90% and a minimum temperature of about 10°C. In general, the growth of A. flavus can be correlated
with the production of aflatoxin except at high temperatures, 40-50°C.
!n different regions of Muranga in Kenya (Hast Africa), mean aflaloxin
levels of about 0.25 ppm in food and 0.1 mg/l in beer have been detected
(IARC, 1972). When common food preparations of Nigeria's principal
food crops were sampled from local market stalls and assessed for aflatoxin
contamination by conventional techniques, the aflatoxin content was not
less than 0.5 ppm in any of the foods (Bababunmi, 1976). Several
industrialized countries such as the United States, Denmark, Britain, and
Italy consider a level of aflatoxin of the order of 0.25 ppm as dangerous
and the contaminated food as unconsumable.
Although the proportional contribution of agriculture to the Nigerian
economy continues to fall, it will continue to be the single most
important sector in the economy for a long time (Aboyadc, 1971). The
export value of cocoa ranks second to that of oil in Nigeria. In 1974,
Nigeria's foreign trade was $3.462 billion. If oil accounted for 80% of the
export value in the 1974-1975 fiscal year, other export products such as
cocoa, groundnuts, and palm products should account for about $700
million. Therefore, if aflatoxin contamination in this class of export
commodities is not eliminated, Nigeria's foreign reserves may diminish
continuously.
Palmotoxin
Isolation of two additional fluorescent toxins from cultures of A.
flavus on unfcrmcnled palm sap (a common West African wine) obtained
from a variety of Elacis yuineensis was reported by Bassir and Adekunle
(1968). Toxicity titrations of pal rnolox iris B 0 and G0 on 6-d-old White
Rock chick embryos indicated that B 0 is as toxic as aflatoxin B t . Recent
results of Uwaifo ct al. (1977) suggest that the structures of the
palmotoxins could be hetetocyclic and may be similar to those of the
aflatoxin family (Asao et al., 1965). Comparative mulagenicily studies by

�696

E. A. BABABUNMI

Uwaifo el v.al. (1978) show that palrnotoxin B() induces microlesions thai
consist of point mutations, in Ames' tester strains of Salmonella
typhimurium. However, the ratio of the mutagcnicity of aflatoxin fi, to
that of palmotoxin B0 is about 6:1.
In Nigeria and several developing African countries, several facilities
and preservation techniques for agricultural products are quite inadequate.
The combination of this unfortunate situation, the natural warm and
moist weather, a dirty environment, human error, and ignorance is
conducive to the growth of A. f/avus and consequently to the elaboration
of mycotoxins (such as aflatoxin and palrnotoxin) on agricultural commodities. It seems to me, therefore, that the problems associated with
mycotoxin contamination of food and agricultural products will remain in
the developing tropical regions of the world for some time, at least.in the
foreseeable future, unless very drastic control measures a' - c initialed.
HERBAL RESIDUES
For years, herbalists and local doctors in tropical Africa have used
herbs and their concoctions to treat various human diseases (Dal/.iel,
1948). In modern times, countries such as Nigeria and Ghana have
intensified their search for authentic medicinal plants ;ind their active
principles. Apart from their use as local medicines, many toxic plant
species are used as food in many parts of West Africa.
Many chemical compounds have been isolated from useful plants of
West Africa and characteri/cd in their pure forms. In this respect,
scientists in the Department of Chemistry of the University of Ibadan have
contributed immensely to the knowledge of the chemistry of active
principles in plants. Toxicological and other biological studies of these
chemicals are, however, scanty. Miller and Miller (1976) staled that the
plant genera Crotolaria, Senecio, Laburnum, and Heliotropium have long
been known to contain carcinogenic substances (IARC, 1976), some of
which arc pyrroli/idine alkaloids.
•; •
FOREIGN TOXIC CHEMICALS
Environmental toxins of this class exist in such forms as medicines,
pesticides, and food additives. With the gradual emergence of some
tropical African countries (for example, Nigeria) from the underdeveloped
to the developing slate, environmental pollution and the presence of
industrial materials such as those used in the processing and packaging of
foods are potential sources of toxins. Common examples in this calegory
are ioni/ing radiation, plastici/ers, adhesives, paraffins, printing inks, and
irea'cd papers. Well-rccogni/.cd environmental toxic (or carcinogenic)
chei lical substances in this tropical area of the world include quinine
(antirnalarial drug), DDT (insecticide), and cyclarnate (food additive).

�TOXINS AND CARCINOGENS IN THt TROPICS

697

Quinine
Malaria is a disease that occurs throughout the tropical and subtropical
countries. It is actually a group of diseases characterized by recurrent
attacks of fever, anemia, and enlargement of the spleen. Malaria can also
occur in temperate climates if the environmental temperature is right for
the protozoan species (e.g., Plasmodium falciparum) to complete their life
cycle in the female Anopheles mosquitoes. The parasite lives in the red
blood cells. There are three forms of the malaria parasite in humans
corresponding to malignant tertian, benign tertian, and quartan malaria. In
the tropics the most common malaria is the malignant tertian, although
the other two varieties have been identified in a very few cases.
Chloroquinc, mcpacrine, and quinine arc drugs that are very effective
in rapidly destroying the parasite in the blood. Chloroquinc (Nivaquine) is
the most widely used antimalarial drug and has been reported to be the
safest. Mcpacrine (Atebrin) can be given only intramuscularly and is not
often used.
Quinine is the oldest of all the antimalarial medicines. It is also the
quickest acting. For many years quinine was the only drug available for
the treatment of malaria. Although quinine has some toxic side effects, it
is still used, especially for cases that are resistant to other drugs. Quinine
was the first alkaloid isolated from the bark of the Cinchona tree. A single
oral dose of about 8 g is regarded as fatal for an adult man. Quinine
poisoning usually results in nausea, headache, visual disturbances, nervous
system and cardiovascular system disorders, and respiratory arrest.

DDT
The insecticidal properties of DDT are well known (IARC, 1974). This
compound has been extensively used as an insecticide and produced
commercially for this purpose since 1943, when a low-cost production
technique was developed. It has been widely used for the control of
numerous insect pests—for example, as a mosquito larvicide and as a
residual spray for eradicating malaria in the tropics. DDT is distributed by
the World Health Organi/ation throughout the world for the prevention of
yellow fever, sleeping sickness, and malaria. Apart from these uses,
quantities of DDT are used for the treatment of peppers, onions,
soybeans, groundnuts, cowpeas, and sweet potatoes, in storage.
Tropical countries such as the Upper Volta and Ghana use at least 500
kg of DDT annually for agricultural purposes. In 1973, research on the
environmental effects of pesticides in the tropics was carried out at the
International Institute for Tropical Agriculture (IITA), Ibadan. The study
was concerned with the effects of DDT (used as a crop protector) on the
fertility of agricultural soil. Cowpca (Vigna unyuiculata var. Prima), which
is a high-yielding legume, was selected in the IITA study because it
requires regular pesticide applications and also because of its growing

�698

C. A. BABABUNMI

importance in tropical agriculture. Since 1970, DDT has been restricted to
uses other than on human and animal foodstuffs in the more advanced
countries. The hepatocarcinogenicity of DDT on oral administration has
been amply demonstrated in several strains of mice. Liver cell tumors were
produced in both male and female mice, and an increased tumor incidence
was reported in some other organs. The most frequent tumor types were
leukemia, rcticulum cell sarcoma, carcinoma of the lungs, and hemangioendothclioma (IARC, 1974).
Cyclamate
Calcium cyclamate (cyclohexylsulfamic acid calcium salt) is still used
as a nonnutritivc sweetener in a large number of soft drinks in many
African countries. The use of cyclamic acid as a sweetener has been
banned in several industrialized' countries because the compound was
suspected of being a bladder carcinogen in the rat.
CONCLUSION
Apart from foods, beverages, and medicines, there are other sources of
potential toxins and carcinogens that are introduced by humans into the
tropical environment, especially in the cities, in such forms as narcotics
and atmospheric pollutants. With the arrival of various industries in big
African cities, inhalation of dust, vapors, and exhausts presents a new
form of danger. Epidemiologic appraisal of these factors is lacking. There
is a need to estimate the total load of toxins and carcinogens in the
tropical environment.

REFERENCES
Aboyadc, O. 1971. Nigeria's economy. In Africa South of the Sahara, 1st ed., pp. 558-563.
London: Luropa.
Asao, T., Buchi, G., Abdel-Kader, M. M., Chang, S. 13., Wick, E. I . and Wogan, G. N. 1965. The
.,
structures of aflaloxins B and G,. ]. Am. Chum. Soi: 87:882-886.
Asplin, [-". D. and Carnaghan, K. 13. A. 1961. The toxicity o\ certain groundnut meals for poultry
with special reference to their effect on ducklings and chickens. Vet. Kec. 73:1215-1219.
Bababunrni, Li. A. 1976. Excretion of af'latoxin in the urine of normal individuals and patients with
liver diseases in Ibadan (Nigeria). In Di'tuclifin and 1'revcnt/on of Cancer, ed. H. E. Nieburgs.
New York: Ueker.
Babdbunni, L:. A., Uwaifo, A. O., and Bassir, O. 1977. Hepatocarcinogeris in Nigerian foodstuffs.
World Rev. Nutr. Did 28: article 44.
Bassir, O. and Adckunle, A. A. 1968. Two new metabolites of Aspcnjillus lluvus (Link). FF.BS Lett.
2:23-25.
Bevan, C, W. 1.. and Hirst, ). 1958. A convulsuil alkaloid of Dioscoreu dunu'torurn.' Chcm. Ind, 4:
103.
.
Crampton, K. l:. and Charlesworlh, I . A. 1975. Occurrence of natural toxins in food. Or. Mvd.
B II. 31:209-213.
Dal/:iel J. M. 1948. Useful plants of west tropical Africa. In i-loia of West Tropical Africa, cds. J.
hutchinson and J. M. Dal/iel. London: Crown Agents for the Colonies.

�TOXINS AND CARCINOGENS IN Tilt TROPICS

699

Goldblalt, L A. 1969. Allatoxln. New Yoik: Academic Press.
IARC. 1971. Liver Cancer. Sci. I'ubl. no. I. l.yon: International Agency for Research on Cancer.
IARC. 1972. Evaluation of Carcinogenic Risk of Chemicals to Man, vol. 1. Lyon: International
Agency for Research on Cancer.
IARC. 1974. Chemical Carcinogencsis l.'ssays. Sci. Publ, no. 10. Lyon; International Agency for
Research on Cancer.
IARC. 1976. Evaluation of Carcinogenic Risk of Chemical* to Man, vol. 10. Lyon: International
Agency lor Research on Cancer.
Joaquim, K. .1973. Nilrosamine contamination of some Nigerian beverages. Ph.D. thesis, Ibadan
University.
Kadis, $., Ciegler, A., and Ajl, S. J. 1972. In Microbkil Toxins: A Comprehensive Treatise, vol. 8,
Fungal Toxins. New York: Academic Press.
Miller, j. A. and Miller, !"..• C. 1976. Carcinogens occurring naturally in foods. Fed. Proc.
35:1316-1321.
Nicholls, L., Sinclair, H. M., and Jelliffe, D. B. 1961. Tropical Nutrition and Dietetics. London:
Bailliere, Tindall &amp; Cox.
Oke, O. L. 1967. Oxalic acid in plants and in nutrition. World Rev. Nutr. Diet. 8:262-303.
Oso, B. A. 1975. Mushrooms and the Yoruba people of Nigeria. Mycologia 67:311-319.
Osuntokun, B. O., Monekosso, G. L., and Wilson, J. 1969. Cassava diet and a chronic degenerative
neuropathy. An epidemiological study. Niger, j. Sci. 3:3-15.
Peters, R. A., Hall, R. J., Ward, P. l:. V., and Sheppard, N. 1960. The chemical nature of the toxic
compounds containing fluorine in the seeds of Dkhapelalum toxicarium. Biochcm. J.
77:17-23,
Pressman, B. C. and Lardy, II. A. 1956. Effect of surface active agents on the latent ATP-asc of
mitochondria. Biochim. B/ophys. Ada 21:458-466.
Uwaifo, A. O., Emcrolu, C. O., and Bassir, O. 1977. Comparative study of the fluorescent
characteristics ol solutions of aflatoxins and palmotoxins in chloroform. /. Agric. Food Chem.
25:1218-1220.
Uwaifo, A. O., Emcrolc, G. O., Bababunrni, E. A., and Bassir, O. 1978. Comparative rnutagcnicity
of palmotoxin U0 and aflatoxin B,. In press.
Wogan, G. N. I975a. Mycotoxins. Annii. Rev. Pliarmacol. 15:437-451.
Wogan, G. N. 1975b. Dietary lactors and special epidemiological situations of. liver cancer in
Thailand and Africa. Cancer Rex. 35:3499-3502.
Received March 12, 1978
Accepted April 3, 1978

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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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on 89

Author

Braun, Daniel C.

Corporate Author
Report/Article TitlB Establishing Environmental Criteria

JOIirnal/BOOk Title

Archives of Environmental Health

Year

™™

Month/Day

September

Color

n

Number of Images

3

DOSCriptOll NOtOS

^'v'n *-• Young filed this Item under the category
"DDT/Human Toxicology and Environmental Fate"
Heading: Pollution Medical Research Conference.

Wednesday, April 11, 2001

Page 1189 of 1242

�lution Medical Research Conferefee

Establishing
j/
Environmental Qrtteria
1

Medical Perspectives
, MD;

reasonable
Nosuggestisthatperson todayofwould
pollution
the
environment not a serious problem,
one which demands the application of
all the intelligent, scientific, and
technical effort we can muster—and
can afford. Physicians are aware of
this. Industrialists, for the most part,
are aware of it. Scientists from a
number of disciplines are working
diligently to define the problems and
to find solutions. Unfortunately, the
greatest deterrent to sound progress
at present comes from those who engage in unscientific exaggerations
while demanding instant results. All
sorts of dire predictions are being
made by all sorts of people, but those
most frightening with respect to
health are being made by persons
who are not physicians.
In their importance to humanity,
the possible effects of pollution on
health far outweigh aspects of aesthetics or comfort. Health is the
Submitted for publication Dec 6, 197% accepted M««h 19,1978.

From the Industrial Health Foundation, Inc.,
PJUfburgh. Mr. tJurgiel it now with Byckman
Edgerley Tomiinfon * Awociatew, 8t Loufe.
Road before t)te Air Pollution Medical Research Conference of the American Medical A&gt;
•ocietion, Chicago, Oct a, 1972,
•
. |^|^ntr»a«eit« to Induitriil Health Paunda.
Won, Inc., 58$1 Centre Av», ntt*b,ur0h, PA
if. 0raun)i '-—-,.:
iron HMlth/Vol 27, Sept 1973

realm of physicians, and so it is important for physicians to know what
substances in the environment are
hazardous to health, or potentially so.
A major problem is that zealots are
calling some situations health hazards when they are in fact merely
nuisances, because this makes the
sequences dire. Sometimes this is
done out of ignorance of the significance of dose-response relationships.
Beyond all others, physicians are
aware of such relationships; they
know that for every substance a certain dosage level is needed to produce
an expected response.
Because health is the most important concern in community contamination, and because the doctor it best
able to understand the physiological
response to various levels of contaminanta, the physician should play a
more important role in public information about and community rosponse to pollution control.
Contaminant* emitted into the
atniosphere arise from maty ********
Sorn^ result from communiiy operations, such at garbage diapoaal and
incineration. Agricultural burninf,
fertilising, and insect-control account
tor tome, and still other* have their
origin in industrial proceaM* &lt;* &amp;•
jjjwration of automobile!, trucks,

Establishing Environment* CrtttftyBraun «t at t||

�buses, boats, and airplanes.
We call attention to the fact that
we said "contaminants" and not "pollutants," The introduction of harmful, impure, or otherwise undesirable
substances into something previously
untainted constitutes contamination,
The result may, for practical purposes, be negligible. It is only when
these substances render the atmosphere or water foul or noxious to
health or life that the word "pollution" is properly applicable.
This may seem to be only an exercise in semantics, but the point of
emphasis is that many people have
fallen into the sad practice of loose
speech and fuzzy definitions in the
whole area of environmental control.
They cry havoc when what is really
needed is merely nuisance abatement.
The fact is that the far-out claims
about air pollution are, at best,
frightening citizens, especially parents, and, at worst, are in a fair way
to leading to panic, simply because of
the lack of precise understanding of
the actual health effects of contaminants in the air we breathe. In a few
well-publicized acute episodes of
near-disastrous magnitude, serious
illness and death have resulted from
polluted air. Therefore, pollution in
high enough concentrations can be
serious. On the other hand, it is perfectly apparent that even in the urban areas of our country the life-span
and general state of health continue
to improve, and so the concentrations
commonly found in urban areas must
be less than disastrous. Again we
return to dose-response relationships.
High enough concentrations can be
harmful to health. Lower concentrations, even though they may offend us
in terms of aesthetics or comfort, can
be completely harmless to health.
Physicians know that the respiratory system is equipped with very
efficient self-cleansing mechanisms,
and can defend against and dispose of
even abnormal amounts of foreign
substances which are inhaled. One
seldom hears or sees this fact referred
to, however, in the talks or feature
articles on air pollution. Physicians
know that the body also has marvelous d«to«ifying mechanisms that can
III Arch Environ Health/Vol 27, Sept 1973

handle low doses of a wide variety of /"Spots and gases. Sulfur dioxide has
substances with no harmful effects, a
in the public press as
fact the public press almost unive%^ ttfe" 'jiq|St 'damaging, corrosive, and
sally ignores.
irritating to humans. Actually, in
f/
It is well, too, to keep in mind that
concentrations it can
"pollution" of the air is an inherent
bronchoconstriction. We
part of the phenomena of nature. Volioians would not be likely to
canic ash has been an important pol- lerm Such effect on airway resistance
lutant, as has smoke from forest fires.
as "corrosive." Careful research on
humans has shown that more than
Ozone in high concentrations is tem13,000/ig of SO, per cubic meter of air
porarily present in the air following
is needed to produce any measurable
lightning storms. Many others could
bronchoconstriction. This can be
be listed.
compared with the governmental
Man, blamed and maligned as the
community air quality standard of
worst polluter, produces only about
80/ng of SO, per cubic meter of air.
0.5% of the total air contamination
The physiological response to SO,
through his inventions and activities.
may be enhanced in the presence of
It is true that this relatively small
particulatefa, moisture, and oxidation,
amount can cause serious problems
because, in contrast to that from natand is also influenced by individual
ural sources, those for which man is
susceptibility. But it is apparent that
responsible are localized and may be
SO, levels in community air must
concentrated.
reach relatively high concentrations
Thus, a power-generating plant
to be deleterious to health.
may emit several hundred tons of sulfur dioxide (SO,) per day, and air
movement across an urban area can
increase the participate loading by
tenfold compared to the air of a nearby rural area.
The articles which follow will deal
in greater depth with specific contaminants and their effects. We wish
merely to touch on a few examples
that, in our judgment, indicate the
areas in which physicians have much
to offer and in which the medical
perspective is essential.
Of the millions of tons of material
thrown into the atmosphere each
year, carbon monoxide (CO), largely
from transportation sources, is the
major pollutant, constituting about
50% of the total loading by man. Its
most serious effects, of course, are to
be expected in persons with chronic
heart and lung disease, but at low
concentrations the effects may be
manifested by visual impairment and
slowed reaction time. To date, most
studies of the effects of CO have employed short-term, high-concentration exposure. Future CO toxicology
must be directed to physiological
changes produced by low levels ov«r
long periods of time.

Other major contaminants are the
oxides of nitrogen and sulfur, hydrocarbons, particulate matter, and* va-~

Hydrocarbons constitute approximately 15% of the total contamination in the ambient atmosphere. The
most important, from the standpoint
of being potential photochemical pollutants, ar j the double-bond olefins,
substituted aromatic hydrocarbons,
and aldehydes and ketones.
Polycyclic aromatic hydrocarbons
are universally present in the atmosphere, and much attention has been
directed to some of them because of
their carcinogenic potential. Thus
far, experimental production of lung
tumors in small animals has not been
accomplished by inhalation, and the
literature presents no clear-cut correlation between the effects of polynuclear aromatic hydrocarbon pollution and lung tumor production in
man. Neitiier does present information indicate any direct health effects
due to the gaseous hydrocarbons in
ambient a&lt;r, but "present information" is still inadequate to state unequivocally ihat there can be none, for
instance, under extremely adverse
meteorological conditions.

Of the teven oxides of nitrogen
known to exist, only two of toxicological importance are present in ambient air-nitric oxide (NO) and nitrogen dioxide (NO,). No data from
either aninal or human studies suggest thai NO is a health hazard at

Establishing Environmental Criteria/Braun et at

�concentrations found in ambient air,
but since it readily oxidizes to NO,, it
possesses potential toxicity. The toxicology &gt;f NO, is difficult to discuss
because of the inadequacy of relevant
data from human studies. An article
that follows will describe the effects of
NO, on schoolchildren in an urban
area. The effects of oxides of nitrogen
at levels of community air pollution
at this time must be considered as
potentially irritating Jlnd possibly
related to chronic pulmonary fibrosis,
but there is insufficient evidence of its
qualitative relationship to them.
With regard to water pollution, the
problems are vastly different today
from those of a few decades ago when
the major concern wns waterborne
bacteria responsible for cholera and
typhoid fever. Development of effective filtration and chlorination techniques has virtually eliminated such
epidem cs. At present, the volume of
industrial and metropolitan wastes is
tremendous and includes an ever-increasing number of synthetic chemical contaminants which did not even
exist a dozen years ago.
Most available data on the effects of
chemicals in water svpplies have
come from experiences in industry.
However, some information has been
obtained from episodes of acute illnesses v^iich result from the presence
of some uncommon natural constituents in crinking water, or accidental
contamination from spillage or jeepage of sc me chemical.
More than 500 new chemicals are
developed each year, and many of
these fir.d their way into our waterways. Sxtch chemicals as nitrates and
nitrites, arsenic and selenium, mercury, organic .carcinogens, and tracemetal antagonists present real challenges to w ater pollution central.
Scientific data on thii relative
importance of heavy metil toxicity
are scarce. The Food and Drug Administration admits to little knowledge regarding levels of toxicity for
metals in foods. Many chemical processes, for instance, use mercury,
which ultimately escapes into waste
water and tends to settle in the sediment of lakes and rivers. Small or-

ganisms not only ingest the metal,
they transform it into a more toxic *
form. Bottom-feeding fish eat the
small organisms and are in turn eaten by larger game fish. Mercury becomes increasingly concentrated with
each successive step. Although mercury probably has been present in
high concentrations in fish for many
years, and possibly has no effect on
persons eating the fish, it is nevertheless a cumulative poison. It exists in
food fishes as methyl mercury, which
is a highly toxic substance that
causes neurological damage, produces chromosomal aberrations, and
has teratogenic effects. Stopping the
discharge of mercury into our waterways is only one aspect of the problem; of greater concern is what to do
with the mercury already lying on
the river bottoms.
Recent studies raise the question as
to whether drinking water which contains minute amounts of carcinogenic
pollutants may, over many years,
contribute directly or indirectly to
cancer in man. Efforts to link organics in drinking water to cancer prevalence have so far been unsuccessful.
Of major consequence with regard
to soil pollution are the pebiicides.
The dilemma of pesticides lies in the
fact that while they do much good,
they threaten a great deal of harm.
They aid in increasing food and fiber
production through protection from
insects, rodents, and weeds, but by
their poisonous nature they may also
endanger human life by long-term,
low-level effects.
Because of recent adverse publicity, the public seems to believe that
pesticides have been spread with
reckless abandon all over the landscape, contaminating all food and
fiber crops and polluting the whole
environment beyond reclamation. As
a matter of fact, it is impossible to
find anything in current popular literature that puta pesticides in a favorable light. If it can be shown that a
pesticide has accumulated in animal
tissue, there is no end to the allegations made against it

For the last decade the dangers of
DDT, its buildup in the environment

as well as in human tissues, have
been a public health issue in this
country. It WM almost completely
banned from use in the United State*
by the Environmental Protection
Agency (EPA) this year. However,
after seven months of hearings by the
EPA during which a stream of scientific witnesses testified, the hearing
examiner found that there was no
conclusive evidence against DDT. In
fact, some of the evidence was clearly
questionable. The World Health Organization has recently sought to
persuade governments to recognize
the fact that although DDT may have
certain hazards, they should not be
allowed to obscure its immense advantages. The World Health Organization feels that, in spite of the adverse publicity, there is no present
justification for abandoning this valuable weapon in the fight against disease.
Physicians, especially those concerned with public health, are becoming more aware of the relationship of
man's well-being to his environment
It is imperative that they maintain a
scientific and professional approach,
and calmly appraise all the facts relating to health, disease, and ecology,
Scientific research is a slow, methodical process, and no amount of hyste
ria, government funding, or legisla
tion will hasten resolution of the
problems of physiological reactions.
This article has merely referred U
some of the aspects of the various
kinds of pollution, meanwhile urging
physicians to become involved, albeit
on a sound and professional basis
While we are all familiar with th&lt;
acute episodes of serious pollution
such as occurred in Donora, Pa, am
the Meuse Valley-and the disastei
at Minamata Bay, Japan, in whid
more than 100 died of mercury poi
soning- we, as physicians must lean
how to evaluate realistically the long
term effects of these pollutants at \o\
levels. With this background, th
medical profession can meet what w
consider to be its obligation to help I
development of proper criteria ft
environmental controls, and in mail
taining the medical perspective,

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              <text>0800</text>
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              <text>Series III Subseries I</text>
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                <text>Kay, Kingsley</text>
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                <text>Environmental Research</text>
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            <name>Date</name>
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                <text>1973</text>
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                <text>Toxicology of Pesticides: Recent Advances</text>
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            <description>The topic of the resource</description>
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                <text>pesticide toxicology</text>
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                  <text>Alvin L. Young Collection on Agent Orange</text>
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                  <text>&lt;p style="margin-top: -1em; line-height: 1.2em;"&gt;The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.&lt;/p&gt;&#13;
&lt;p&gt;For more about this collection, &lt;a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a"&gt;view the Agent Orange Exhibit.&lt;/a&gt;&lt;/p&gt;</text>
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          <description>The series number of the original item.</description>
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              <text>Series III Subseries I</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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                <text>Kimbrough, Renate D.</text>
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          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
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                <text>Drug Metabolism Reviews</text>
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          <element elementId="40">
            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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                <text>1982</text>
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            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Disposition and Body Burdens of Halogenated Aromatic Compounds: Possible Association with Health Effects in Humans</text>
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            <name>Subject</name>
            <description>The topic of the resource</description>
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                <text>CDC</text>
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                <text>health effects</text>
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                <text>pesticide toxicology</text>
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        <name>ao_seriesIII</name>
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