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Hazards and Exposures
Associated with DDT
and Synthetic Pyrethroids
used for Vector Control
World Wildlife Fund
January 1999
ACKNOWLEDGMENTS
WWF appreciates the contributions and critical comments of the many experts who created and
reviewed this report. Primary authors are Dr. Michael Smolen, WWF US; Dr. Susan Sang, WWF
Canada; and, Dr. Richard Liroff, WWF US. Additional contributions came from Dr. Donald
Mackay and his coauthors on the exposure model; Dr. Lizbeth Lopez-Carillo, Intituto Nacional de
Salud Publica; and, Yvonne Martin Portugues-Santacreu. Special thanks are also due to Dr. Polly
Hoppin for initiating this project while at WWF US. The editorial assistance of Stephen Leahy and
Julia Langer is also acknowledged.
WWF would also like to thank the North American Commission for Environmental Cooperation
and The J.W. McConnell Family Foundation (Canada) for their generous funding for this project
and WWF’s work to conserve biological diversity.
Hazards and Exposures Associated with DDT and Synthetic Pyrethroids used in Vector Control is part of
WWF’s project to gain a legally-binding agreement on Persistent Organic Pollutants (POPs). The
exploration of DDT use in malaria control is aimed at documenting not only the hazards and
exposures to humans and wildlife but also alternatives that protect both biodiversity and human
health. WWF’s ultimate goal in this area is to have DDT banned globally.
Front cover photo credits: Peregrine falcon: US Fish and Wildlife Service; Mother and child from
Manang District in Nepal: Galen Rowell
Other related publications:
Resolving the DDT Dilemma: Protecting Biodiversity and Human Health
WWF Canada and WWF US
June 1998
52 pages
Available in Spanish and English
Also available on-line at www.worldwildlife.org
A Model and Assessment of the Fate and Exposure of DDT Following Indoor Application
Katie Feltmate
April 1998
125 pages
Disease Vector Management for Public Health and Conservation
Dr. Patricia Matteson et al.
In Press
Approx. 200 pages
All publications available for $10 each (Cdn. or US) from:
WWF Canada WWF US
245 Eglinton Ave. East, Suite 410 1250 24th Street NW
Toronto, ON, M4P 3B7 Washington, DC, 20037-1175
EXECUTIVE SUMMARY The largest remaining legal use of DDT is for
control of disease vectors. Although DDT is
This report summarizes the current state of used for interior spraying of households, a
knowledge regarding the health and WWF-commissioned mass balance model
environmental effects of DDT and synthetic shows that most of it ultimately ends up
pyrethroids. Currently, DDT’s only official use, outdoors where it joins the pool of DDT in
as specified by the World Health Organization general circulation. Significant human exposure
(WHO), is for the control of disease vectors in occurs from the DDT applied indoors which
indoor house spraying – although other (illegal) ends up in food. Infants and those responsible
uses are suspected. Synthetic pyrethroids are for house cleaning are particularly exposed to
increasing in popularity among managers of residues on floors and walls.
vector control programs as alternatives to DDT,
either for indoor spraying or for impregnating Concern about DDT has generally been derived
bednets. from its reproductive toxicity in animals, as
demonstrated by eggshell thinning. The
Much of the traditional debate over DDT and mechanisms by which DDT (DDE) causes
DDT-alternatives has focused on effects such eggshell thinning are associated with the
as cancer (carcinogenicity), impacts on inhibition of prostaglandin synthesis, an
reproduction, and gross birth defects. important initial step in shell creation. The
Traditional toxicological testing has attempted result—extremely thin eggshells that crack in
to discern these effects through tests that rely nests—has brought several species to the brink
on using high doses of chemicals. This report of extinction. DDT’s estrogenic and/or anti-
takes a broader view. In addition to looking at androgenic properties can contribute to
these traditional effects, it examines current feminization or demasculinization, resulting in
knowledge about the effects of DDT and altered behaviour, reduced fertility, and birth
synthetic pyrethroids on the endocrine, nervous, defects. Other developmental effects may
and immune systems and behavior, and it involve incomplete urogenital development and
emphasizes potential hazards from low doses of undescended testicles arising from the prenatal
chemicals. disruption of testosterone.
Concentrations in humans of DDT and its The biological processes controlled by the
breakdown product, DDE, are clear barometers endocrine system—including the immune,
of exposure. Although DDT levels are nervous, and reproductive systems—are
decreasing in parts of the world, there are common to all animals. As such, the adverse
populations of people and wildlife that health impacts identified in wildlife and
experience concentrations of DDT and DDE laboratory animals from exposure to DDT and
above critical levels. For instance, investigations other classes of pesticides serve as indicators of
in Mexico and South Africa reveal that human potential hazards to humans.
breast milk contains DDE at concentrations
that exceed the guidelines for the acceptable Synthetic pyrethroids and DDT have been
daily intake by infants set by the WHO. associated with irreversible effects on the
Moreover, studies have shown that the length developing nervous system. Specifically, DDT
of lactation (milk production) decreases with and some synthetic pyrethroids alter the
higher DDE body burdens in human mothers, proportions of neuroreceptors in the developing
thus depriving infants of benefits provided by brain of neonates, leading to hypersensitivity
breast feeding. In addition, DDE and behavioural abnormalities.
concentrations in some bird species are still
high enough to cause reproductive failure.
i
They can also reduce the efficiency of neural to mention possible trans-generational
signal transmission. consequences of chronic human exposures.
Laboratory studies describing such possible
By interfering with the endocrine system, hazards are summarized in this paper. WWF
specifically lymphocyte function, humoral urges pesticide manufacturers and public
response, and thymus weight, DDT and agencies to conduct collaborative research to
synthetic pyrethroids contribute to suppression analyze the possible hazards from chronic
of immune responses. Symptoms of decreased human exposure to synthetic pyrethroids.
immune competency include, among others,
changes in antibody production and the time it In addressing DDT and pesticides which may
takes to respond to infections. These raise be proposed as alternatives to it, WWF urges
concerns about the vulnerability of certain application of the ―precautionary principle‖ that
portions of the population, such as the elderly already forms the basis of a growing number of
and the very young. international treaties and agreements.
According to the ―precautionary principle,‖
WWF recommends the following directions for when substantial scientific evidence suggests
future research on endocrine-disrupting good reason to believe that an activity,
chemicals such as DDT and synthetic technology, or substance may be harmful,
pyrethroids: action should be taken to prevent harm. In
other words, if an activity raises credible threats
Low-Dose Testing: WWF recommends that of harm to the environment or human health,
traditional government-mandated tests of precautionary measures should be taken even if
chemicals, which historically have focused on cause and effect relationships have not yet been
administering high doses of chemicals, usually fully established scientifically.
to adult animals, must be revised to take
account of the hazards associated with the The scientific findings summarized here provide
exposure of fetuses and embryos to extremely support for WWF’s view that DDT should be
low doses of chemicals that disrupt the characterized by the WHO and international
hormonal systems of the body. Organisms assistance agencies as a ―pesticide of last
frequently are exposed chronically to such doses resort,‖ to be used only when no other vector
in the environment. control methods (including other pesticides) are
available and likely to be effective. WHO and
Transgenerational Effects: Only recently other organizations should take this step based
have attempts been made to assess more on the additional evidence about the human and
insidious and often overlooked efforts related to biodiversity impacts of DDT that has been
pesticide exposure. Mushrooming scientific gathered since the last major consideration of
understanding of the influence of hormonal this issue by WHO’s scientific experts in 1993.
(endocrine) systems on the development and
health of humans and wildlife indicates that This change in WHO’s characterization should
future consideration of DDT/DDT-alternatives be an interim step en route to a global ban on
must be broadened to address very significant production and use of DDT no later than 2007,
effects whose causes are harder to discern. The under the auspices of the global treaty on POPs
impacts of chemicals on developing nervous (persistent organic pollutants) that is now being
systems, immune systems, and behavior must be negotiated (with mid-to-late 2000 as the targeted
taken into account with special attention given completion date). The 2007 deadline coincides
to exposure in the womb. with Mexico’s commitment, pursuant to the
North American Regional Action Plan for
Synthetic Pyrethroids: The existing literature DDT, to end its use. Mexico is one of the
on use of synthetic pyrethroids for world’s few producers of DDT; if Mexico is
impregnating bednets and spraying houses fails
ii
willing to make such a commitment, other
nations should also be willing and able to do so.
WWF’s initial report on DDT, ―Resolving the
DDT Dilemma: Protecting Biodiversity and
Human Health,‖ published in June 1998, brings
together in summary form the new information
on the impacts of DDT and other pesticides
used for vector control contained in this report,
and six case studies of successful vector control
projects which do not rely on DDT. This
information provides the rationale for moving
away from DDT and other pesticide-dependent
malaria programs toward ―bio-reliant‖ vector
management techniques. That report and the
complete texts of the case studies (to be
published as ―Disease Vector Management for
Public Health and Conservation‖ in early 1999)
are available from WWF.
iii
iv
TABLE OF CONTENTS
PART I – DDT AND OTHER CHEMICALS USED IN VECTOR
MANAGEMENT PROGRAMS .......................................................................................1
A Brief History.....................................................................................................................1
Insecticides Currently in Use ...............................................................................................1
Chemical Properties .............................................................................................................5
Persistence and Transport Characteristics............................................................................5
DDT in the Arctic Food Web...............................................................................................5
Bioaccumulation in Organisms ............................................................................................6
The Role of the World Health Organization ........................................................................9
PART II – HEALTH AND ENVIRONMENTAL EFFECTS .....................................10
Introduction ........................................................................................................................10
Acute and Chronic Toxicological Effects ..........................................................................16
Reproductive Effects ..........................................................................................................18
Effects on the Nervous System ..........................................................................................22
Effects on the Immune System ..........................................................................................24
DDT and Cancer ................................................................................................................31
Summary ............................................................................................................................32
PART III – EXPOSURE AND ITS IMPLICATIONS .................................................33
Levels of DDT in Humans .................................................................................................33
Levels of DDT and Effects in other Species ......................................................................34
Routes of Exposure ............................................................................................................35
Synthetic Pyrethroids .........................................................................................................38
Interpretation of Human Exposure Data ............................................................................38
PART IV – RECOMMENDATIONS FOR RESEARCH ............................................38
Low-Dose Testing ..............................................................................................................39
Testing for Transgenerational Effects ................................................................................39
Assessment of Synthetic Pyrethroid Exposure to Children
and the Developing Fetus from Bednets ...........................................................................40
In Closing – The Precautionary Principle ..........................................................................40
v
I. DDT AND OTHER The effects of DDT on wildlife reproduction
and its residues appearing in food products that
CHEMICALS USED IN had been sprayed with DDT became evident in
VECTOR MANAGEMENT the 1960s. Long term studies showed that DDT
PROGRAMS was found at alarming levels in many animal
species including fish, birds, and mammals.
A Brief History Many birds such as peregrine falcons, California
condors, and bald eagles with high levels of
DDT (dichlorodiphenyltrichloroethane) is an DDT in their bodies began producing weak
organochlorine insecticide used mainly to eggshells, which were crushed upon incubation.
control mosquito-borne malaria. DDT‘s The result was a decline in the bird populations
insecticidal properties were discovered in the and a threat to their very existence. These
1930s by Swiss chemist Paul Müller. findings led to DDT use restrictions and bans in
Considered harmless to mammals this odorless, the U.S., Canada, and most European countries
tasteless, white crystalline chemical was used in the early 1970s. DDT is now banned in 34
during the Second World War for crop countries and severely restricted in 34 (IEM on
protection as well as protection of troops from POPs, Annex II).
malaria and typhus. DDT‘s characteristics of
insolubility in water, persistence, long half-life
of 10-35 years and high-contact toxicity made it Insecticides Currently in Use
appear to be the ideal insecticide. As a The World Health Organization (WHO)
consequence, Müller was awarded the Nobel approves use of DDT in controlling malaria,
Prize in 1948. Only a few years later, Swiss provided several conditions are met, including
scientists confirmed the connection between limiting its use to indoor spraying, taking
unborn and functionally-impaired calves whose appropriate safety precautions, and using
mothers had been grazing on pastures that had materials that meet WHO specifications. Four
been sprayed with DDT. Previously, U.S. major groups of insecticides are available for
agricultural researchers had linked similar indoor spraying: organochlorine chemicals
severe impairments in calves whose mothers had (DDT), organophosphates, carbamates, and the
been eating feed salted with DDT for pest synthetic pyrethroids (Table I-1). The
control (IEM on POPs, Annex II). Still others undesirable effects of DDT are widely known;
had found that young roosters treated with DDT they have driven the restrictions on DDT that
had severely underdeveloped testes and failed to have occurred to date and are responsible for
grow the normal combs and wattles roosters use DDT being targeted in international POPs
for social display (Colborn et al., 1996). negotiations. The organophosphates and
Regardless of these effects, DDT‘s efficacy and carbamates are acutely toxic to humans, and
low-production costs made it the most widely pose a high hazard in particular to those who
used agricultural insecticide in the world from work with them (Herath, 1995). The synthetic
1946 to 1972. Total world production of DDT pyrethroids are not as toxic as the carbamates or
during this period has been estimated from 2.8 organophosphates, and are widely used as an
million tonnes to more than 3 million tonnes alternative to DDT or used to impregnate
(IEM on POPs, Annex II). bednets. Because most reports of wide-scale
applications of pesticides for vector control
involve DDT or the synthetic pyrethroids, the
discussion that follows focuses mainly on these
pesticides.
1
Table I-1: Toxicity of Vector Control Insecticides
†
Insecticide LD50* Toxicity to Environmental Toxicity Source
Oral Humans/Mammals
(Rat)
Organochlorines
DDT 113-800 Can affect liver, kidneys, Toxicity very low to birds, very 1-4
mg/kg immune system. high to fish and aquatic
Neurotoxicant, probable invertebrates, nontoxic to bees.
carcinogen, teratogen, Chronic effects (eggshell
reported reproductive/ thinning, etc) may be significant.
endocrine disruptor. Extremely persistent and
bioaccumulative.
Dieldrin 37-87 Can affect liver. Extremely persistent and 2-8
mg/kg Neurotoxicant, probable bioaccumulative.
carcinogen, reported
endocrine/reproductive
disruptor.
Endosulfan 18-160 Can affect kidneys, liver, Toxicity moderate-high to birds, 1-3
mg/kg blood, parathyroid gland. very high to fish and aquatic
Neurotoxicant, suspect invertebrates, moderate to
mutagen, possible bees. Persistence moderate in
teratogen, reported soil, varied in water, low in
endocrine/ reproductive plants. Bioaccumulation may be
disruptor. significant in aquatic organisms.
HCH (lindane) 88-190 Can affect liver, kidney, Toxicity extremely low- 1-4
mg/kg pancreas, testes, nasal moderate to birds, high-very
mucous membrane. May high to fish and aquatic
affect immune system. invertebrates, high to bees.
Neurotoxicant, probable Persistence high in most soils
carcinogen, reported and in water, varied in plants.
endocrine/reproductive Bioaccumulation significant in
disruptor. aquatic organisms.
Organophosphates
Chlorphoxim >5000 Possible neurotoxicant. No sufficient data found. 5, 8
mg/kg
Chlorpyrifos 95-270 Can affect cardiovascular Toxicity moderate-very high to 1
mg/kg and respiratory systems. birds, very high to fish and other
Neurotoxicant. aquatic organisms. Poses
serious hazard to honeybees.
Persistence moderate in soil.
Bioaccumulation in aquatic
organisms.
Fenitrothion 250-800 Neurotoxicant, reported Toxicity low-high to birds, 1, 3, 9
mg/kg endocrine/reproductive moderate to fish, high to
disruptor. crustaceans, aquatic insects,
and bees. Not persistent.
Moderately bioaccumulative.
Malathion 1000- Can affect immune Toxicity moderate to birds, very 1-3
10,000 system, adrenal glands, low-very high to fish, high to
mg/kg liver, blood. Neurotoxicant, aquatic invertebrates and
suspect mutagen, reported honeybees. Low persistence.
endocrine/ reproductive
disruptor.
2
Table I-1 Continued
†
Insecticide LD50* Toxicity to Environmental Toxicity Source
Oral Humans/Mammals
(rat)
Pyraclofos 237 No sufficient data found. No sufficient data found. 5
mg/kg
Phoxim 300- Neurotoxicant. Short residual life. 5, 8, 10
>2000
mg/kg
Temephos 1226- Can affect liver. Potential Toxicity moderate-high to birds, 1
13,000 to cause significant moderate-very high to fish and
mg/kg neurotoxic effects with other aquatic organisms, high to
long-term exposure. bees. Persistence low-
moderate in soil, low in water,
high in plants. Potential to
bioaccumulate in aquatic
organisms.
Carbamates
Bendiocarb 34-156 Neurotoxicant. Toxicity moderate to birds, 1
mg/kg moderate-high to fish, high to
bees. Persistence low in soil.
Not bioaccumulative.
Carbosulfan 91-250 Neurotoxicant. Toxicity moderate-high to birds, 19
mg/kg very high to fish and other
aquatic organisms.
In soil rapidly transformed to
carbofuran, which is moderately
persistent. Low potential to
bioaccumulate.
Propoxur 100 Can affect liver. Toxicity high-very high to birds, 1, 4
mg/kg Neurotoxicant, probable low-moderate to fish and other
carcinogen, teratogen. aquatic species, high to
honeybees. Persistence low-
moderate in soil. Low
bioaccumulation.
Synthetic
Pyrethroids
Bifenthrin 54-70 Neurotoxicant, possible Toxicity moderate to birds, very 1, 3, 4
mg/kg carcinogen, reported high to fish and other aquatic
endocrine/reproductive species, high to bees.
disruptor. Persistence moderate. Possible
bioaccumulation.
Cyfluthrin 869- Can affect kidney. Toxicity low to birds, high to 1, 9
1271 Neurotoxicant fish, other aquatic organisms,
mg/kg and bees. Virtually non-
persistent to moderately
persistent. Moderate
bioaccumulation.
ß-Cyfluthrin 450 No sufficient data found. No sufficient data found. 11
mg/kg
-Cyhalothrin 56-144 Neurotoxicant, reported Toxicity very low to birds, very 1, 3
mg/kg endocrine/reproductive high to fish, other aquatic
disruptor. organisms, and bees.
Persistence moderate in soil.
Bioaccumulation unlikely.
3
Table I-1 Continued
†
Insecticide LD50* Toxicity to Environmental Toxicity Source
Oral Humans/Mammals
(rat)
Cypermethrin 150- Can affect liver, thymus, Toxicity very low to birds, very 1, 4
(includes ) 4123 adrenal glands, lungs, high to fish and other aquatic
mg/kg skin. Neurotoxicant, organisms, high to bees.
possible carcinogen. Persistence moderate in soil.
Moderate potential to
bioaccumulate in aquatic
organisms.
Deltamethrin 31-5000 Neurotoxicant, reported Toxicity low to birds, high to 1, 3, 9
mg/kg endocrine/reproductive laboratory fish, very high to
disruptor. bees. Moderate potential to
bioaccumulate.
Ethofenprox (or >42,880 Can affect liver, kidney, No sufficient data found. 3-5, 12
etofenprox) mg/kg thyroid. Possible
carcinogen, reported
reproductive/ endocrine
disruptor.
Permethrin 430- Can affect liver, immune Toxicity very low to birds, high 1, 4, 9
4000 system. Possible to fish and other aquatic
mg/kg carcinogen organisms, very high to bees.
High potential for
bioaccumulation.
* LD50 indicates the amount of toxicant necessary to kill 50% of the organisms being tested. LD50 is used
to measure the acute oral (and dermal) toxicity of a chemical. The lower the LD50 the more poisonous the
chemical. Different sources frequently reported different LD50s (rat, oral) for the same chemical. In
general, we used range values from the most recent source. When values differed greatly between two
sources, we gave range values incorporating all LD50s given in both sources.
† Sources varied in their interpretation of the environmental toxicity of each pesticide. Rather than making
our own interpretation, we quoted directly from the most recent or most reliable source.
1. Extension Toxicology Network (EXTOXNET): A Pesticide Information Project of Cooperative Extension Offices of
Cornell University, Oregon State University, the University of Idaho, and the University of California at Davis and the
Institute for Environmental Toxicology, Michigan State University (http://ace.ace.orst.edu/info/extoxnet/). July, 1999
(access date).
2. Colborn T. Endocrine disruption from environmental toxicants. In: Environmental and Occupational Medicine, Third
Edition (Rom WN, ed). Philadelphia, PN: Lippincott-Raven Publishers, 1998;807-816.
3. Brucker-Davis F. Effects of environmental synthetic chemicals on thyroid function. Thyroid 8(9):827-856, 1998.
4. United States Environmental Protection Agency, Office of Pesticide Programs. Pesticidal chemicals classified as known,
probable or possible human carcinogens (http://www.epa.gov/pesticides/carlist/). July, 1999 (access date).
5. Meister RT, Sine C, eds. Farm Chemicals Handbook ‗99. Willoughby, OH: Meister Publishing Company, 1999.
6. United States Environmental Protection Agency, Integrated Risk Information System (IRIS) (http://www.epa.gov/iris/).
July, 1999 (access date).
7. Spectrum Laboratories Inc (http://www.speclab.com/). July, 1999 (access date).
8. Hayes WJ, Laws ER, eds. Handbook of Pesticide Toxicology. San Diego, CA: Academic Press, Inc., 1991.
9. Andersson L, Hemming H, Johnson A, Kling L, Tornlund M. Hazard assessments of chemical alternatives to POP
pesticides. Annex 1 to Chapter 3, pp. 202-279 in: Alternatives to Persistent Organic Pollutants (KEMI Report 4/96). Solna,
Sweden: Swedish National Chemicals Inspectorate and Swedish Environmental Protection Agency, 1996.
10. Lu FC. A review of the acceptable daily intakes of pesticides assessed by WHO. Regulatory Toxicology and Pharmacology
21(3):352-364, 1995.
11. Chavasse DC, Yap HH, eds. Chemical methods for the control of vectors and pests of public health importance
(WHO/CTD/WHOPES/97.2). World Health Organization, 1997.
12. Food and Agriculture Organization/World Health Organization, International Programme on Chemical Safety. Etofenprox
(JMPR 1993). Pp. 215-232 in: Pesticide residues in food—1993: Part II—toxicology (WHO/PCS/94.4). World Health
Organization, 1994.
4
Chemical Properties 10 to 35 years after its last application. For
example, an Oregon (U.S.) orchard still had 40
DDT is available in several different forms: per cent of the original DDT used 20 years later.
aerosol, dustable powder, emulsifiable DDD has also been shown to be even more
concentrate, granules, and wettable powder. persistent in soils, sediments, and waters, lasting
Technical grade DDT is actually a mixture of as long as 190 years (IEM on POPs, Annex II).
three isomers of DDT, including the p,p‘-DDT
isomer (85%) with the o,p‘-DDT and o,o‘-DDT These compounds do not remain in the soil, but
isomers present in much lesser amounts are transported into the general environment by
(ATSDR, 1994). The content of these isomers is the processes of volatilization, through wind and
important because the o,p‘(ortha-para) isomer is water erosion. Although more than 20 years
said to be five to nine times less toxic in tests have passed since the last applications of DDT,
with rats than the p,p‘(para-para) isomers. While cotton soils are estimated to be volatilizing 110
DDT is highly resistant to degradation, some tonnes of DDT and its metabolites annually into
microbes can degrade DDT into a variety of the atmosphere. These small particles are
metabolites. Among the more important of these transported long distances on air currents, and
is DDE and TDE (DDD). The latter is also are returned to the land surface by precipitation.
manufactured as a commercial product (IEM on
POPs, Annex II). DDT in the Arctic Food Web
There has been very little local use of DDT in
Persistence and Transport the high arctic, therefore the presence of DDT in
Characteristics arctic biota is indicative of the global or
hemispherical transportation of this compound.
At present, most of the millions of tonnes of
DDT has been found at various concentrations
DDT that have been produced in the past
in all trophic levels of the arctic food chain.
continue to be transformed and redistributed
Table I-2 is a summary of DDT concentrations
throughout the environment. DDT and its
found in the lower trophic levels of the arctic
metabolites have been detected in virtually all
marine food web. Table I-3 shows
media throughout the world. An extremely
concentrations of DDT in the blubber of arctic
stable chemical compound, 50 per cent of the
mammals.
DDT sprayed on a field can remain in the soil
Table I-2: DDT Concentrations (ppb lipid wt.) in Marine Biota in Various Locations in
High Arctic [adapted from Jensen, J., K. Adare, and R. Shearer (eds.) Canadian Arctic
Contaminants Assessment Report. (Ottawa, Ontario, Canada: Department of Indian Affairs
and Northern Development, 1997)]
Biota Region Total DDT
Epontic Particles Ice Island 20-70
Barrow Strait 150-360
Zooplankton Ice Island 8-150
Barrow Strait 2-20
Amphipods
Pelagic Ice Island <350
Pelagic Barrow Strait 3-60
Benthic Arctic Ocean 2,200-25,900
Benthic Barrow Strait 15-1,590
5
Biota Region Total DDT
Fish
Arctic Cod Lancaster Sound 66-120
Barrow Strait 15-255
Turbot Cumberland Sound 626-1,044
Beaufort Sea 659-1,1251
Four-horn Sculpin Wellington Bay 93
Cambridge Bay 1,225
Hall Beech 135
Bivalves
Clams Sanikiluaq 34
Septentrion sp Manitounuk Sound 13
Table I-3: Mean Concentrations (ppb wet wt.) of Total DDT in Blubber of Arctic Mammals
[adapted from Jensen, J., K. Adare, and R. Shearer (eds.) Canadian Arctic Contaminants
Assessment Report. (Ottawa, Ontario, Canada: Department of Indian Affairs and Northern
Development, 1997)]
Species Female Male
Ringed Seal 473 959
Harp Seal 486 NA
Beluga Whale 1,940 4,974
Narwhal NA 3,232
Walrus 744 1,744
Adult Polar Bear (Bernhoft et al., 1997) 372 340
Water runoff provides another mode of Bioaccumulation in Organisms
transportation. DDT sticks to soil particles by
the process of adsorption. These particles are Bioaccumulation Potential
transported to lakes and rivers and are the
principal route by which lakes and streams Bioaccumulation reflects the relationship
become contaminated. In an experimental plot between how much is taken into an organism by
of cotton, runoff waters transported 2.8 per cent exposure versus how much is lost through
of the DDT applied in six months. metabolism and excretion. The key in pesticide
exposure scenarios is whether the rates of
Under tropical conditions, residues continue to metabolism and excretion remove enough of the
be detected in major water bodies in the substance to prevent a gradual increase in the
Philippines despite DDT‘s restricted-use status. organism. If the rates of metabolism and
Fish, as well as duck eggs, from lake areas also excretion are not rapid, an organism will
show residues (IEM on POPs, Annex II). accumulate ever-increasing concentrations,
While DDT will evaporate and photo-oxidize adding to the concern about chronic, low-dose
from soil surfaces to a certain degree, it is a exposures.
robust and long-lived chemical compound. Even Chemicals that are water soluble are more easily
when its use is banned globally, DDT and its excreted, as well as more easily mobilized to
various metabolites will continue to travel in the sites responsible for metabolism of the
winds and waters and accumulate in the bodies compound. On the other hand, a chemical with
of the world‘s organisms for decades to come.
6
high solubility in lipids (fats, oils, or waxes) has America‘s Great Lakes basin despite restrictions
bioaccumulation potential. Such lipophilic on its use in the United States and Canada. It
chemicals easily move into cells and are appears that much of the DDT currently being
sequestered in fat where they can become more deposited in the basin is atmospherically
persistent. DDE is an example of a lipophilic transported from Central and South America.
chemical that resists enzymatic degradation and,
Even though the concentration of DDT in
therefore, rapidly bioaccumulates. DDT is also
plankton is 1/100 part per million, the flesh of a
lipophilic, however, it is more readily degraded
fish-eating bird in the same lake system may
and excreted from the body.
contain 630 times that concentration (Colborn et
al., 1990).
Bioaccumulation in the Great Lakes Food
Web
DDT continues to be deposited in North
Table I-4: Bioaccumulation of DDT in Lake Ontario Food Web (Colborn et al, 1990)
Species Concentration (ppm wet weight)
Plankton 0.01
Mysis 0.03
Pontoporeia 0.10
Sculpin 0.40
Smelt 0.40
Lake Trout 1.10
Herring Gull 6.30
Synthetic pyrethroids are also lipophilic though a single topical application of deltamethrin
they are more like the isomers of DDT in that (0.75%), cypermethrin (10%), or cyhalothrin
they can be metabolized to more water soluble (4.5%) to dairy cows was detectable in both the
forms that can then be excreted. Furthermore, cows‘ blood and milk for 28 to 35 days
the sites where they can be metabolized are not (Bissacot et al., 1997). In these situations,
limited to the liver and therefore, metabolism is bioaccumulation results in much lower peak
much quicker. For example, the elimination concentrations since the differences between
half-life for deltamethrin in plasma of the rat is exposure and intake are not widely different
33 hours (Anadon et al., 1996) with almost from metabolism and excretion. The concern
complete elimination from the body by day 4 would be if the exposure is periodic, with a span
(Ruzo et al., 1978). Cypermethrin is more shorter than the rates of excretion. Chronic, low-
resistant to elimination; 90% is lost in the first dose exposures may lead to slightly increased
four days, however, total elimination may take concentrations in the body. There is little known
as long as 17 to 26 days (WHO Working Group, about the pharmacokinetics of the synthetic
1992). pyrethroids.
Synthetic pyrethroids (permethrin, deltamethrin)
DDT Bioaccumulation in Humans
are rapidly distributed in the body (Anadon et
al., 1991, 1996). The primary sites of deposition In surveys around the world of human blood, fat
are the central nervous and peripheral nervous tissue, and breast milk, DDT and its metabolites
systems, which can have concentrations of are found in substantial quantities (Thomas and
permethrin ranging from 1.5 to 7.5 times higher Colborn, 1992; Jensen, 1990). For example,
than those observed in plasma. In another study, Table I-5 reviews concentrations of two isomers
7
that are known endocrine disruptors. Since DDT result of a combination of a pesticide-rich food
is very lipophilic, it accumulates in all fats, source (breast milk) and a lower total body fat
including the 3% fat found in breast milk content in the baby. As the baby matures, fat
(Rogan et al., 1986). The quantity of DDT and accumulations increase the available pool which
DDE varies with the age of the individuals with in effect dilutes the DDT/DDE enriched fetal fat
young individuals having higher concentrations reserve.
than older individuals. This is probably the
Table I-5: Concentrations of o,p’-DDT or p,p’-DDE (endocrine-disrupting isomers of DDT)
in Breast Milk of Women (standardized to ppm fat)
Country # Year o,p’- p,p’- Citation
Women DDT DDE DDT
Canada 497 1995 0.003 0.22 Newsome et al., 1995
U.S.A, New York 7 1985-87 - 0.54 - Schecter et al., 1989
Mexico, Veracruz 43 1994-95 0.27 5.02 6.44 Waliszewski et al., 1996
Mexico, Mexico-City 50 1994-95 0.14 0.59 0.93 Torres-Arreola et al., 1998
Germany 150 1985-87 - 0.75 - Schecter et al., 1989
Spain, Madrid 51 1991 - 0.60 0.66 Hernandez et al., 1993
Norway 20 1988 0.97 Skaare et al., 1988
United Kingdom 193 1989-91 - 0.40 - Dwarka et al., 1995
France 20 1990-91 - 2.18 - Bordet et al., 1993
Slovakia 50 1994 1.20 Prachar et al., 1996
Yugoslavia,
Krk Island 33 1986-87 - 1.10* - Krauthacker, 1991
Labin 20 1986-87 - 0.55* - Krauthacker, 1991
Croatia 50 1981-82 1.90 Krauthacker et al., 1986
Nigeria 10 1987 0.99 Atuma and Okor, 1987
Nigeria, Benin 35 1981-82 - 1.1 - Atuma and Vaz, 1986
Kenya 68 1983-85 1.73 Kanja et al., 1986
New Guinea, Papua 41 1990 - 0.45 0.89 Spicer and Kereu, 1993
Uganda 143 1992-93 0.06 2.35 Ejobi et al., 1996
Zimbabwe, Kariba 39 1994 13.60 25.26 Chikuni et al., 1997
Australia, Victoria 60 1995 0.96 Quinsey et al., 1995
India 60 1985-86 1.43 7.28 Zaidi et al., 1989
India 25 1988 2.00 Tanabe et al., 1990
Jordan, Amman 15 1989-90 0.23 2.04 3.31 Alawi et al., 1992
Saudi Arabia 115 1995-96 - - 0.27 Al-Saleh et al., 1998
Turkey 104 1995-96 - 2.01 2.36 Cok et al., 1997
Thailand, Bangkok 3 1985-87 3.61 Schecter et al., 1989
Vietnam 7 1985-87 6.70 Schecter et al., 1989
Note: Methodologies used to quantify isomers varied, however they allow for comparisons of geographical
differences.
* Median
could reach those of the mother in the first three
A breast feeding baby can acquire months of breast feeding. The levels of DDT in
concentrations of lipophilic chemicals at the blood begin to decline at about 3 years of
extraordinary rates. Mes et al. (1984) estimated age, again probably reflecting the shift in diet to
that babies could acquire 1.8 micrograms of a less contaminated food, and an increase in new
p,p‘-DDE per gram body fat (or 1.8 ppm) by the fats.
14th week of breast feeding from breast milk
alone. Furthermore, the infant‘s DDT levels
8
Based on observations in South Africa of DDT applications for vector control had significantly
(and DDT derivatives) in breast milk, Curtis higher DDT levels in their sera than those in
(1994) estimated that a baby fed entirely by regions where no spraying occurred.
breast milk exceeds the allowable daily intake
Lactational transfer is not limited to DDT or
(ADI) for DDT (0.02 mg/kg), as determined
DDE. Any pesticide that enters the body can be
by FAO/WHO (1985), by 5 to 18 times. Rogan
excreted in breast milk (Rogan and Ragan,
and Ragan (1994) estimated that over a nine-
1994). Synthetic pyrethroids have also been
month period of breast feeding, an infant can
reported in the milk of dairy cows when
acquire 21.5 mg of DDE based on the 90th
pesticides were applied as a part of an
percentile level. Such estimates identify breast
ectoparasite control program. Deltamethrin,
feeding as a principal source of exposure to
cypermethrin, or cyhalothrin were reported in
DDT and DDE. It must be pointed out that this
milk within 24 hours of application (Bissacot
exposure of the newborn coincides with
and Vassilieff, 1997), with concentrations of
development of their brains (Eriksson, 1997), so
0.51, 0.36, and 0.19 ppm, respectively. The
such exposure has implications for neural
organophosphate pesticide, chlorfenvinphos,
development, behaviour, and susceptibility to
another topical treatment for ectoparasites in
insecticides later in life (Johansson et al., 1996).
cattle, was recorded to vary from 1.18 to 10.40
This concern for exposure during early
ppb in milk from cows in Kenya (Kituyi et al.,
development will be discussed in more detail
1997). Only recently has attention been focused
later in the paper.
on the transfer of synthetic chemicals in human
The DDT and DDE a nursing baby acquires or cow milk, and therefore, it is not known what
from breast milk come directly from the low the magnitudes of transfer are for commonly
background exposures and accumulation over used pesticides.
the years in the mother. In one study, levels of
The fact remains that this lactational transfer is
DDE were found to be 17% lower in women
the rule of pharmacokinetics of synthetic
who had breast fed previously as compared to
chemicals, and not the exception. The concern
those who had not. This was confirmed in
increases as the transfer rate and concentration
studies of women who were followed through
of the chemicals increases, which is related to
two pregnancies, where there was a 23%
both the application rate, frequency, and the
difference in DDE levels between their first and
bioaccumulation potential of the chemicals.
second child.
The quantity also changes with the length of the
nursing period – declines in DDE in milk of
The Role of the World Health
20% at six months, and a 40% decline by the Organization
18th month of nursing (Rogan et al., 1986). The National health authorities determine the nature
amount of DDT and DDE in the bodies of the of their malaria control efforts, including
women participating in this study was the result whether or not DDT is to be used, based on
of low background exposures beginning early in specific national circumstances, priorities, and
their lives. It was not the result of accidental or political considerations. However, they do
agricultural exposures. receive and rely on guidance from the WHO.
The persistence of lipophilic chemicals is cause The WHO‘s Expert Committees collect and
for concern because exposure to low analyze information and the WHO supports and
concentrations over an extended period of time participates in the development of new methods
may lead to substantial burdens later in life. In and strategies for disease control, issuing
an analysis of DDT exposures associated with recommendations and technical guidelines (Bos,
indoor application of DDT for malaria control in pc).
KwaZulu, Africa, Bouwman and colleagues In 1992, governments signed a WHO-sponsored
(1991, 1993, 1994) found that household World Declaration on the Control of Malaria
members in regions that used indoor pesticide
9
and endorsed a Global Strategy for Malaria II. HEALTH AND
Control. Prior to this time, DDT was considered
the insecticide of choice and it was thought that
ENVIRONMENTAL
there were no acute toxic health impacts to EFFECTS
applicators nor any significant risks to humans.
However, the new Global Strategy recognized Introduction
the need for an integrated approach that
A new set of concerns is emerging regarding the
involved early diagnosis and prompt treatment;
impact of DDT and other pesticides on the
selective and sustainable preventive measures,
endocrine system. These are a significant
including vector control; prevention, early
addition to scientists‘ and regulators‘ knowledge
detection, and containment of epidemics (WHO,
of more traditionally recognized acute and
1993).
chronic effects. Cancer, reproductive, and
By 1993, against the backdrop of a report on teratogenic endpoints have historically been the
high levels of DDT in breast milk of women and basis for public health use approvals; the
the occurrence of cancer, a WHO expert group growing body of evidence of effects on immune
re-examined DDT. They concluded that the function, the nervous system, and certain
evidence on the adverse effects of DDT as a aspects of reproduction in both humans and
result of indoor residual spraying was wildlife, has not been considered or examined
insufficient. However, because new and safer thoroughly. Such effects are not the result of
insecticides such as synthetic pyrethroids were genetic, behavioural, or immune competence.
available, the experts indicated that ―DDT no These health endpoints are primarily mediated
longer merits being considered the only mutations, but arise from problems in gene
insecticide of choice‖ (WHO Report Series 857, expression. These result in functional changes
1995). that affect future performance, whether it be
physiological, reproductive, neural, through the
The group also urged closer examination of such
neural and endocrine systems. This section
health issues as cancer and exposure of babies to
outlines the latest information regarding the key
contaminated breast milk. A background paper
mechanisms by which pesticides used in vector
for the group had concluded that ―it can no
control can cause endocrine disruption with
longer be confidently stated that DDT anti-
potential for reproductive, neural, immune
malarial spraying is harmless to human
impairment/dysfunction and cancer.
health‖(Curtis, 1994).
In 1997, reflecting growing interest at various Overview of The Endocrine System
international forums in the reduction and
The endocrine system in humans and other
elimination of POPs, the World Health
organisms consists of glands that secrete
Assembly adopted a resolution to reduce
hormones into the bloodstream to regulate body
reliance on insecticides for control of vector-
processes. Components of the endocrine system
borne disease by promoting Integrated Pest
that control development and function include
Management and ensuring that DDT was used
the ovaries and testis, thyroid, adrenals, and
only within programs that take an integrated
parts of the pancreas gland and their many
approach (WHA, 1997).
hormones, including estrogen, testosterone, and
In late 1998, an Expert Committee will develop thyroxine. Hormones are specialized molecules
recommendations for consideration at the that travel through the bloodstream and interact
January 1999 meeting of the WHO Executive with a specific target cell (Table II-1). These
Board (Bos, pc, 1998). chemical messengers trigger a complex series of
events that choreograph development and
function and are involved in:
10
sexual differentiation: regulating the rates of influencing neural development, such as that
cell division leading to the construction of required for constructing the hypothalamus,
tissues and organs that eventually determine cerebellum, and other regions of the brain.
future function, such as sperm production The endocrine system operates at very low
and ovulation; chemical concentrations. In the womb, for
controlling the development of cells that example, natural hormones cause effects at
make up the immune system, thus affecting concentrations of trillionths of a gram.
future ability to combat disease; and,
Table II-1: Selected Hormones: Sources and Effects
Hormone Source Effects on
Estrogen ovary Reproductive tract development and function;
Expression of secondary sexual characteristics; brain
development and behaviour
Testosterone testis Reproductive tract development and function;
Expression of secondary sexual characteristics; brain
development and behaviour
Thyroxine thyroid Brain development and behaviour; growth; metabolism
Mullerian-Inhibiting Substance (MIS) testis Development of reproductive tract
The release of hormone molecules is carefully events that are irreversible (Colborn and
regulated and balanced by a variety of feedback Clement, 1992).
mechanisms. In each case, the response depends
Because of the critical role the endocrine system
upon the binding together of a hormone
plays in directing development and maintaining
molecule with a specific receptor (protein).
the physiological homeostasis of organisms
Together, they initiate specific responses in the
throughout life, it is ―highly conserved.‖ In
cell through the expression of genes that are
other words, distantly related groups like
coded on the cell‘s DNA, yielding enzymes that
reptiles, insects, birds, mammals and humans
influence specific biochemical pathways. This
share almost identical hormones and receptors,
results in changes in rates of cellular activity,
as well as similar biological responses. As a
shifts within reproductive cycles, or increases in
result, certain effects observed in the
rates of cell divisions.
development of particular species can convey
The endocrine system is extraordinarily potentially important lessons regarding the
complex. For example, cells in different tissues hazards of chemicals to other species, including
respond differently to the same hormone. In humans. These similarities among conserved
brain tissue, estrogen can alter behaviour, while systems form the basis for the testing of
the same hormone, when ―plugged into‖ chemicals on animals in laboratory settings and
receptors in cells lining the reproductive tract, the drawing of inferences from those tests about
can initiate changes in a reproductive cycle such hazards to human health. They also raise
as cell proliferation. Moreover, cells of the same concerns about observed effects in wildlife and
tissue may respond differently to the same the implications for human health.
hormone at different stages of development.
More importantly, hormone-receptor Endocrine Disruption: The Newly-
interactions occurring early in development Emerging Science
frequently lead to a cascade of developmental Human-made chemicals can interfere with or
11
perturb the endocrine system at both high and organism‘s immune, reproductive, and other
low doses. Such perturbations have been systems perform.
reported in numerous laboratory studies and in
In addition, endocrine disruption is not limited
field studies involving exposure of wildlife to
to interference with receptors. Other
chemicals released into the environment. The
mechanisms involve alterations in
well-documented story of diethylstilbestrol
neurotransmitters (nervous system), cytokines
(DES), a pharmaceutical administered to
(immune system), and expression of liver
pregnant women to increase the probability of
enzymes whose presence alters hormone
successful births, exemplifies the
concentrations in the blood. However, little is
―transgenerational‖ effects of estrogen-like
known about the mechanisms involved with
compounds, including human-made chemicals
these pathways, including possible effects from
released into the environment (Bern, 1992). The
pesticides used in vector-control programs and,
effects of the confirmed estrogen-mimic DES on
except for disruption of neurotransmitters, these
mothers were minimal, and their babies were
processes will not be discussed in this paper.
born ―healthy.‖ However, some of the exposed
children developed a variety of anomalies later The developing offspring is the most sensitive
in life which subsequent research has linked to target of endocrine disruption since much of the
the disruption of their endocrine system in utero neural, reproductive, and immune development
by DES. occurring in the womb continues into early
childhood (Bern, 1992). Many human-made
chemicals can cross the placental barrier,
Endocrine disrupting chemicals work by a
thereby allowing the mother‘s body burden of
variety of mechanisms:
chemicals to be shared with her developing
1. As agonists, they impersonate natural offspring. Doses of chemicals during
hormones by binding to receptors and embryonic, fetal, and early post-natal
initiating a new cellular response. development can be the highest exposures
2. As antagonists, they bind and block the encountered throughout life.
receptor, thereby making these regulatory
switches unavailable to signals from the Chemicals vary in their endocrine-disrupting
body‘s naturally produced hormone effects since they interact with different
messengers. receptors and target cells, accumulate at
3. By altering concentrations of natural different rates, and have different binding
hormones through promoting or interfering affinities. In field and laboratory studies,
with the breakdown of the hormone by the perturbations to the endocrine system leading to
liver‘s enzyme system. developmental, reproductive, behavioural,
4. By altering the number of receptors in immunological, and physiological changes have
developing tissue types, thereby been demonstrated. Examples include thyroid
predisposing these tissues to abnormal dysfunction in birds (Moccia et al., 1986), fish
responses later in life. (Moccia et al., 1981), and mammals (Brouwer et
al., 1989); growth or developmental
The net result of any of these disruptive irregularities in fish (Jobling et al., 1996, Gray
mechanisms is a perturbation to systems that are and Metcalfe, 1997; Leatherland, 1993), reptiles
critical for the creation and maintenance of the (Guillette and Crain, 1996; Guillette et al.,
body plan that has been molded by natural 1994), turtles (Bergeron et al., 1994), and
selection over countless generations. These mammals (Gray and Kelce, 1996; Gray et al.,
perturbations are not from a genetic mutation 1994); behavioural abnormalities in birds
but from confused chemical messenger systems (Barron et al., 1995); demasculinization and
that alter how and when genes are ―expressed.‖ feminization of males in invertebrates (Ellis and
These changes in expression can lead to Pattisina, 1990), fish (Davis and Bortone, 1992;
―functional deficits‖ – changes in how well an Gimeno et al., 1996), birds (Fry and Toone,
1981), and mammals (Facemire et al., 1995);
12
defeminization and masculinization of females endpoints, whereas perturbations involving
in fish (Monosson, 1997), and compromised subtle shifts to performing neural, endocrine,
immune systems in birds (Grasman et al., 1996) and developmental pathways are conceptually
and mammals (Ross et al., 1996). different. While not ignoring the traditional
acute and chronic (cancer, teratogenesis) effects
Key Considerations for Health Effects with which DDT and other pesticides have been
Determinations associated, this paper deals primarily with the
effects related – in one way or another – with
DDT and its metabolites have received
disruption of the endocrine system.
considerable attention in part because of their
persistence and ability to accumulate in fat.
Concentrations are easy to quantify, and DDT‘s Some important points that must be
association with eggshell thinning in wild-bird considered when evaluating the health risks
species has given it a high visibility. Research to involved:
identify the pathways and mechanisms through
which DDT and several other similar Chemical exposures during development can
organochlorine compounds act has led to the create a lifetime legacy.
discovery of steroid hormone agonistic and Alterations to the function and fate of cells or
antagonistic receptor binding behaviour, the tissues during development are irreversible.
more subtle effects on nerve performance, and Once a specific cell type is differentiated and
alterations to developmental processes. the cells are calibrated to perform at a level set
Furthermore, there is growing interest in by the embryonic environment, the fate of the
possible linkages to immune suppression, organism is set. All of the age classes from
behavioural effects, and breast cancer. Less is developing fetus through young adolescent are
known about some of the newer pesticides used delicate stages during which chemical exposure
in vector-control programs. can undo the balance designed by generations of
evolution.
For instance, there has been research into
synthetic pyrethroids to determine LD50s and For instance, if chemical exposure occurs during
high-dose cancer screening but only recently has a critical pre-natal/neonatal developmental
interest been directed at determining their window it can cause alterations to an
potential for interacting with the immune individual‘s neural and chemical messenger
system. Preliminary work with neural systems and have deleterious long-term effects.
development further indicates that synthetic These may include diminished performance of
pyrethroids behave like DDT in causing subtle physiological, reproductive, or immune
changes during the development of the processes and therefore may not become
cerebellum, neural transmissions, and behaviour apparent unless there is an unusual stress. Food
(Eriksson, 1992, 1997). deficiencies, extremes in weather or climate,
and other environmental stressors exacerbate an
In order to arrive at some conclusions
otherwise tranquil physiology.
concerning the environmental and public health
safety of DDT or its substitutes, much more
research needs to be done to understand the Biologically active materials have many
more subtle ‗health endpoints‘ discussed in this „targets‟ and produce a range of effects.
paper. However, the scientific literature offers Multiple targets and varying mechanisms are not
compelling evidence of effects resulting from unusual with biologically active molecules. The
exposure to these pesticides that deserve serious isomer o,p‘-DDT provides a good example. It
consideration. These effects reflect alters the sodium/potassium channel in a neuron,
impingement on aspects of biological function alters calcium balance in gap junctions, and is
that are very different from the mechanisms an estrogen agonist. Effects documented involve
associated with cancer and teratogenesis. The anatomical and morphological changes to the
latter are extreme and easily detectable brain and reproductive system, aspects of
13
immune suppression, increased or decreased a causal link. For instance, when DDT or a
neural sensitivity to stimuli, behavioural synthetic pyrethroid, like deltamethrin, are
changes, and possible increased susceptibility to administered to an adult animal, disruption to its
some types of cancer. DDT‘s modes of action neural performance is observed in a dose-
and effects should not be considered dependent fashion. Furthermore, as the chemical
exceptional. is metabolized, sequestered in fat, or excreted
from the body, the effects diminish. However,
effects on the offspring that result from
All living organisms share biochemical
developmental events may not be so easily
strategies.
linked.
This biological reality means that an adverse
effect on the ion pump of an insect should be Eriksson and colleagues (Eriksson, 1992;
expected to similarly affect an ion pump of a Eriksson et al., 1992) conducted an elaborate
mammal. Many structures involved in cellular series of experiments that demonstrated that
and intercellular functions are shared even DDT and some synthetic pyrethroids altered
among distantly related species. For example, brain structure and function. Neural tissue
mitochondria power cells in all animals and appeared to become more hyperactive when the
sodium/potassium channels pump ions in nerve animals reached adulthood. But no trace of DDT
cells in invertebrates and all vertebrates. Subtle was found in their brain tissue one month after
differences are more often related to alternate administration. If investigators were looking for
pathways or processes that arise with increasing a cause/effect relationship involving DDT, no
complexity than with alterations of basic connection would be made.
structures.
Exposure to DDT early in development has also
In addition, similar biological processes are at been found to modify the sensitivity of the
play throughout an organism. For example, neurons. When offspring were exposed to
neurons are distributed throughout the body and paraoxon, the metabolite of permethrin,
perform a variety of specialized and isolated hyperexcitability occurred at unexpected and
functions. Chemicals that alter basic biological seemingly unexplainable low doses although no
functions, like polarization of neurons or DDT residues were detected (Johansson et al.,
destruction of synaptic messengers, can lead to 1996).
various effects. Likewise, estrogen mimics
Even if a chemical is rapidly metabolized and
acting through the estrogen receptor have
excreted, it cannot be assumed there is no health
different effects in different tissues and stages in
risk, especially when there is chronic exposure.
the life cycle. Recent research indicates that
For instance, cypermethrin is an example of a
estrogen receptors appear in a wide variety of
rapidly metabolized synthetic pyrethroid that, if
tissues, e.g. brain, testis, lung, bone cells, and
briefly present at a critical time during
kidney.
development, can lead to measurable changes in
the immune system later in life.
Chemical culprits may not leave “footprints
in stone.”
Alterations in neural or chemical messenger
Causal relationships between chemicals and
systems can lead to many subtle changes in
effects are difficult to establish when dealing
the body.
with complex animals that have long life spans,
Alterations in neural or chemical messenger
diverse lifestyles, and multiple chemical
systems can lead to permanent change in cells
exposures. The time from the initial damage to
and tissues resulting in diminished capacities or
the manifestation of the effect may take many
altered outcomes. For instance, exposure to
years or even skip a generation and only be
DDT during development can perturb the
expressed in offspring exposed in utero. If the
processes which give an individual the ability to
chemical is present along with an observed
fight pathogens or parasites later in life;
effect, then the chances increase of establishing
14
enzymatically metabolize foreign chemicals in Adverse effects at the individual level have
the liver; rally the immune system to contain population-level implications.
and destroy foreign materials; respond to Traditional assessment of health effects focuses
environmental cues to coordinate reproduction; on the effects to the individual and rarely
and assimilate a wide variety of stimuli to extends to populations or ensuing generations.
coordinate behavioural reactions to the However, considering the potential for
environment and the other individuals in it. developmental effects to alter behavioural,
reproductive, and immune systems, more far-
reaching implications need to be considered. For
Even low-dose exposure is biologically
instance, immune suppression has population-
relevant.
level implications ranging from reduced
Developmental windows are briefly opened
effectiveness of immunization programs,
during which time chemical messengers signal
persistence of pathogens in reservoirs in the
the developmental fate of cells and tissues.
population from which new outbreaks can rise,
Neither the natural nor impostor chemical cues
increased parasite loads, and illnesses of longer
required to trigger these changes need to be
duration.
overwhelming. For instance, mice exposed
perinatally to a single dose of 0.5 mg/kg DDT While behaviour has much plasticity of
(Eriksson et al. 1992, 1997) experienced expression and is a difficult parameter to assess,
changes in brain development at an estimated 15 the kinds of effects that pesticides may have
parts per trillion in the brain tissue. This is in include those that lead to decreases in memory,
contrast to the (high) dosing regimes of 10, 20, learning, tolerance of stress or changes in
40, or 100s of mg/kg that are typical of surroundings, and alterations in aggression
experiments conducted to assess acute and levels.
chronic health effects of DDT using rodents.
Endocrine Disrupting Pesticides
Very little research has been done using low,
environmentally relevant and biologically Many pesticides have been identified as endocrine
meaningful doses. New research to determine disrupting chemicals, including dicofol,
hormone-receptor-mediated effects of synthetic vinclozolin, chlordecone, toxaphene, 2,4-D, 2,4,5-
chemicals emphasizes that the effects observed T, atrazine, dieldrin, heptachlor, mirex and
at low doses usually reflect alterations to the chlordane. Various pesticides used in vector
normal functioning of biological systems that control are also considered endocrine disruptors,
are not observed when the system is namely DDT and its metabolites, parathion,
overwhelmed by doses hundreds of thousands of methoxychlor, lindane, endosulfan, chlorpyrifos,
malathion, diazinon, carbaryl, and some of the
times more concentrated (vom Saal et al., 1997).
synthetic pyrethroids. However, since current
While such extremely high doses are useful in
regulations governing pesticides the world over do
identifying some behaviours of chemicals and not require screening of pesticides for endocrine
hazards from cancer, they miss the impacts on disruption, per se, it is not known for certain how
functional responses through modifications to many currently-used pesticides are endocrine
regulatory systems. Low-dose effects need to be disruptors. Those identified thus far are so labeled
considered when identifying possible threats because of the basic research efforts of
from pesticides. independent laboratories.
15
Endocrine Disruption by DDT and Methoxychlor
Concerns about the effects of DDT and its metabolites on the health of wildlife and humans have a long
history. Besides well-documented effects on eggshell thinning, a variety of abnormalities are seen in male
sexual development. These effects were often described as estrogen-like. One of the chemicals in
technical-grade DDT, the isomer o,p’-DDT, is an estrogen hormone mimic that competes for the estrogen
receptor. It binds to the receptor and activates biochemical pathways as if it were estrogen. Exposure has
been shown to lead to the early appearance of the first ovulation and loss of fertility. Target tissues where
effects have been seen include the mammary gland, uterus, cervix, vagina, prostate gland and seminal
vesicles.
Recently, Kelce and coworkers (1995) have shown that the primary metabolite of DDT, p,p’-DDE, is a
potent androgen receptor blocker (antagonist). It binds to the androgen receptor, blocking a switch critical
for the development of normal males. Male mice exposed to DDE in utero are feminized and
demasculinized.
Methoxychlor and its metabolites provide an example of how a pesticide can disrupt the chemical
messenger system. Methoxychlor is an estrogen agonist, but is weak compared to its metabolite.
Methoxychlor itself has a very low binding ability to the estrogen receptor. However, methoxychlor is
metabolized in the liver to 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) (Cummings, 1997).
When HPTE binds to the estrogen receptor, it initiates the same biochemical pathways as estrogen,
resulting in increases in specific enzyme activity and changes in both uterine weight and fertility.
The effects of methoxychlor vary with concentration (ATSDR, 1994b; Cummings, 1997; Cummings and
Metcalf, 1995a; Martinez and Schwartz, 1991; Eroschenko and Cooke, 1990) in a fashion that highlights
the chimerical nature of endocrine disruption. At high doses, where most laboratory testing is done, one
finds cellular degeneration in the liver and kidneys and an increased incidence of hepatocellular
carcinomas in the liver of mice and rats. At lower doses of exposure during prenatal/early-postnatal
development, females develop an increased incidence of precocial vaginal opening, hypertrophied uterine
and oviductal epithelium, persistent vaginal estrus, decreased implantation rates, and an acceleration in
the transport of embryos through the reproductive tract. Exposure of adult males to methoxychlor
decreases spermatogenesis, while changes in uterine weight and increases in atretic follicles are common
in females. Within six hours of exposure, there is a significant increase in uterine weight indicating the
quick responses to methoxychlor. Changes in adult behaviour have also been demonstrated. When
pregnant mice are exposed from day 11 to 17 of pregnancy, their male offspring display increased
territorial markings when they grow to adulthood. Such alterations occur in a dose-dependent manner and
emphasize potential developmental effects during brain development (vom Saal et al., 1997).
Methoxychlor has been linked to endometriosis (Cummings and Metcalf, 1995b), a disease in women
where uterine endometrial tissue grows outside the uterus. At low doses, methoxychlor sustains
endometriosis, as does estrogen. At higher doses, methoxychlor exacerbates the development of
endometriosis and can potentially contribute to its recurrence. Endometriosis, once instigated, is
maintained by the estrogen-mediated endocrine system, and an agonistic chemical mimic would serve as
another stimulus to the maintenance or growth of the tissue.
For those women currently suffering from endometriosis, the relative importance of exposure to synthetic
estrogen agonists, as compared to other causal factors, has not been determined.
Acute and Chronic Toxicological from controlled laboratory studies with human
Effects volunteers, non-human primates, and other
mammalian species. Overall, these studies
Acute Toxicity indicated that DDT may cause a number of
adverse effects in humans ranging from acute
The toxicological effects of DDT on human toxicity to cancer (Hayes, 1982).
health have been evaluated using information
16
Symptoms of acute poisoning include For instance, in California Sea Lions living on
paraesthesia, tremors, confusion, headache, the Channel Islands, one of the world‘s most
fatigue and vomiting. Dermal exposure does not DDT-contaminated areas, early termination of
seem to be associated with illness and irritation pregnancy and premature births have been
(Hayes, 1982). observed. Premature pups had two to four times
higher concentrations of DDT than full-term
DDT is highly toxic to fish and aquatic
pups (DeLong et al., 1973).
invertebrate species, slightly to partially non-
toxic to birds, and moderately to slightly toxic to There are indications that long-term exposure to
mammalian species (See Tables II-2 & II-3.). DDT may reduce sperm counts and lower
DDT has also been associated with premature fertility rates, and may cause other reproductive
births, absorbed fetuses and lower birth weights. problems.
Table II-2: Toxicity of DDT and its Derivatives to Selected Aquatic Organisms
(adapted from Ritter et al., 1995)
Species Compound Temperature 96-h LC50
(C) (µg/L)
Estuarine/Marine Organisms
Crangon setemspinosa DDT 20 0.40
(shrimp)
Mysidopsis DDT 25 0.45
(mysid shrimp)
Cyprinodon variegatus DDT 15 2.00 (48-h)
(sheephead minnow)
Morone saxatillis DDT(77%) 17 0.53
(striped bass) DDE 2.50
Freshwater
Daphnia magna DDT 20 1.10 (48-h)
(water flea)
Palemonetes kadiakensis DDT 21 2.30
(glass shrimp) TDE 0.68
Pteronarccys california DDT 15.5 7.00
(stonefly naiad) TDE 380.00
Salmo gairdneri DDT 20 42.00
(rainbow trout) DDE 12 32.00
TDE 12 70.00
Pimephales promelas DDT 18 13.20
(fathead minnow)
Lepomis macrochirus DDT 18 6.30
(bluegill) DDE 17 240.00
TDE 24 42.00
17
Table II-3: Acute Toxicity of DDT and its Derivatives to Selected Avian Species
(adapted from Ritter et al., 1995)
Species Compound/Purity % Age LD50
(mg/kg body weight)
Callipepla californica DDT (TG) 6 months 595
(California quail) TDE (>95) >760
Anas platyrhynchos DDT (77.2) 3 months >2240
(mallard duck) TDE (>95) >2000
Phasianus cochicus DDT (>99) 3 months 1334
(pheasant) TDE (>95) 3-4 months 386
Chronic Toxicity Reproductive Effects
The pathways over which DDT is metabolized are
similar among rodents and humans. However, in Eggshell thinning
controlled studies where adult humans were given In North America, widespread declines in
DDT, DDE, or DDD, the DDT to DDD
predatory and fish-eating bird populations
pathway accounts for the vast majority of the
including peregrine falcons, brown pelicans,
principal urinary metabolite (DDA). This further
highlights the fact that the primary source of bald eagles, white eagles, eagle owls, sparrow
DDE detected in humans is that acquired in the hawks, gulls, terns, and osprey, became known
diet as DDE. Little, if any, DDE is produced in 1960s. The cause is attributable to eggshell
from the metabolism of DDT in humans thinning and the subsequent effect on
(ATSDR, 1994). reproductive success. Thinner eggshells crack
easily under normal nesting conditions, resulting
In adult experimental animals, chronic exposure in embryo deaths. Researchers found an inverse
to DDT has led to effects on the liver, kidney, relationship between eggshell thickness and the
and nervous and immune systems. Effects on the p,p‘-DDE residue in the eggs of various species
nervous system include tremors (in rats at doses of birds. While DDT is often accompanied by
of 16-32 mg/kg/day over 26 weeks, in mice at other pollutants such as PCBs, dioxins, and
doses of 6.5-13 mg/kg/day over 80-140 weeks), mercury, laboratory tests and comparisons
changes in cellular chemistry in the central among the effects of various pollutants in the
nervous system (monkeys at doses of 10 eggs of 14 species of birds have concluded that
mg/kg/day over 100 days) and loss of p,p‘-DDE showed the greatest correlation with
equilibrium (monkeys at doses of 50 mg/kg/day eggshell thinning. Also, investigations of the
for up to 6 months) (ATSDR, 1994). mechanism of action of p,p‘-DDE-induced
The toxic effects of DDT on the liver in adult eggshell thinning found little evidence of other
study animals include changes in liver cell pollutants, in particular PCBs, having similar
physiology, increased liver weight, and effects (see How DDT Weakens Eggshells, page
increased liver enzyme activity. Kidney effects 19).
include adrenal gland hemorrhage. The
immunological effects include reduced antibody
formation and reduced levels of immune cells
(ASTDR, 1994).
18
How DDT Weakens Eggshells A catastrophic drop in bald eagle population
recruitment – from 1.26 young per breeding area
Eggshell formation in birds involves the transfer
of large amounts of calcium from the blood to in 1966 to as low as 0.46 in 1974 in
the eggshell gland lumen. Concurrently, an equal northwestern Ontario – led to the eagle‘s
amount of carbonate ions is required for the shell designation as an endangered species in Canada
calcification to occur. Carbonate ions are and the United States. Reproductive success as
predominantly produced by carbonic anhydrase measured by chicks per nest increased not long
activity in the shell gland mucosa and, to a lesser after Canada and the U.S. banned DDT in the
extent, are derived from blood (Skimkiss and early 1970s. By 1981 nest success improved to
Taylor, 1971). Calcium transport from the blood
to the shell gland lumen is stimulated by the
1.12 young/nest in northwestern Ontario (Grier,
presence of sodium and bicarbonate in the gland 1982). In the U.S., where there were fewer than
lumen. During the eggshell formation process, 500 pairs of bald eagles in the lower 48 states in
the calcium level is regulated by a calcium- 1963, bald eagle population size dramatically
binding protein, calmodulin. Calmodulin and rebounded to more than 5,000 pairs by 1996. In
other calcium-binding proteins are critical 1995, the eagle was down-listed from
intercellular regulators that act as receptors for endangered to threatened status, under the U.S.
calcium ions. Various enzymes can interact with
Endangered Species Act.
the calcium-calmodulin unit to initiate a
biochemical or physiological response. The However, despite the recovery of bald eagles in
activity of calmodulin and other calcium- some parts of the U. S. and Canada, there are
dependent 3’,5’cAMP phosphodiesterase was areas where bald eagles still experience poor
found to be strongly inhibited by DDT during an
in vitro assay (Hagmann, 1982). reproductive success. A study of the bald eagle
population along the Columbia River estuary, in
This finding provided support for the hypothesis the states of Washington and Oregon, found that
by Lundholm (1987) that an inhibition of
eagles in only 30% of the occupied breeding
calmodulin is involved in DDE-induced eggshell
thinning. This hypothesis correlates with many territories were successful in fledging young.
toxic properties of this chemical class since Also, the analysis of egg contents revealed the
other organochlorines such as DDT, PCBs, and presence of DDE along with other
dieldrin can also inhibit calmodulin activities organochlorines and metals. The concentration
(Feyk and Giesy, 1998). However, it does not of DDE ranged from 4 to 20 ppm wet weight
correspond with specificity of eggshell thinning of (these concentrations are within the range of 15-
DDE. The most current hypothesis is that the 20 µg DDE/g, known to cause reproductive
mechanism of DDE-induced eggshell thinning
involves an inhibition of prostaglandins (PGs) by failure in predatory birds, and well above the 5
the shell gland mucosa. PGs synthesis is ppm critical level). The examination of eggshell
stimulated by progesterone, and plays an thickness showed that on average 10% of the
important role in the control and regulation of eggs had thinner eggshells than pre-DDT. In
reproduction in birds (Lundholm and Bartonek, some cases, the eggshell thickness was up to
1992). The synthesis of PG is inhibited by p,p’- 44% thinner than pre-DDT average thickness.
DDE in duck shell gland mucosa, both in in vitro The analysis of prey fish samples from the
experiments and following in vivo experiments.
But p,p’-DDT, o,p’-DDT, and o,p’-DDE did not
estuary showed that all had detectable DDE
inhibit the synthesis of prostaglandins. p,p’-DDE concentrations ranging from 0.1 to 0.5 ppm wet
may induce eggshell thinning by inhibiting PG mass (Anthony et al., 1993).
synthesis and thereby reducing carbonate ion
North America‘s peregrine falcon suffered
secretion to the shell gland lumen. Prostaglandin
E2 stimulates the transport of carbonate ions similar declines in reproductive success.
from shell gland mucosa to the gland lumen. If Heavily contaminated with organochlorine
this is the case, inhibition of prostaglandin residues, DDT in particular, populations of
synthesis by p,p’-DDE would hamper carbonate peregrine falcons in Rankin Inlet, NWT,
ion transport and thereby retard calcium declined to 35% of their pre-DDT numbers by
transport (Lundholm, 1994). the 1970s (Kiff, 1988). Like bald eagles,
peregrine falcon populations have recovered as
a direct result of the DDT ban. However, due to
19
DDT and its metabolite‘s long half-life and related laboratory experiment, when gull eggs
persistence, they continue to affect were injected with DDT at concentrations
reproduction. Even in remote areas like Rankin comparable to those found in contaminated
Inlet in Northwest Territories, peregrine seabird eggs, abnormal development of ovarian
eggshell fragments collected from 54 clutches tissue and oviducts in male embryos was
were 15% thinner (0.306 mm) between 1991 induced (Fry and Toone, 1981; Fry et al., 1987).
and 1994 than the average pre-DDT shell
For a short period after conception, embryos
thickness (i.e. 0.360 mm). Also, 28% of all
have the potential to become male or female
samples showed thinning equal to or greater
depending on whether a developmental ‗switch‘
than critical levels associated with reproductive
is thrown or not thrown. Approximately 15 days
failure and population decline in this species
after conception for rats and after 56 days in
(i.e., 17% of average pre-DDT shell thickness).
humans, a slight pulse in testosterone signals the
Analysis in 1991 showed that 10% of the
male reproductive organs to begin developing
population had eggs with DDE concentrations
and the existing tissues fated for the female to
exceeding the critical levels (Johnstone et al.,
self-destruct. The ―default route‖ of
1996). Peakall et al. (1975) noted that eggs with
development – if the developmental switch is
DDE residues of 15 to 20 µg/g would
not thrown – is for the organism to develop as a
experience reproductive failure. In addition to
female. The testosterone pulse is triggered by
North America, peregrine falcon eggs collected
the Y-chromosome in mammals. The resulting
in 1990 in Zimbabwe had 10% thinner shells
chorus of endocrine messengers begun by
compared to pre-DDT values (Hartley et al,
testosterone directs the elaboration of the
1995). Other raptors such as hawks, eagles, and
structure (anatomy), shape (morphology),
falcons in Zimbabwe experienced reproductive
function (physiology) and behaviours necessary
failure as well. In 1981, Thomson predicted that
for the genetically-determined sex. Disruption
many raptor species in Zimbabwe would
of hormone messengers during this stage of
become extinct within 15 years unless the use of
development can cause feminization and
DDT was curtailed (Thomson, 1981, cited in
demasculinization of males or defeminization
Hartley, 1994).
and masculinization of females. This can result
Long-term studies of brown pelicans in the Gulf in functional abnormalities, altered behaviour,
of California, Mexico, identified reproductive reduced fertility, and birth defects such as
problems under conditions of both DDE incomplete urogenital development
exposure and food stress. Some years, pelicans (hypospadias) and undescended testicles
failed to breed or after mating they deserted (cryptorchidisms).
nests and abandoned eggs and young. DDE
The period of gestation to shortly-after-birth has
residues in the adipose tissue of breeding a large number of windows where hormone
pelicans ranged up to 2050 ppm (Keith and signals are critical for proper development. For
Mitchell, 1993). instance, at various times during this period, the
differentiation of regions of the brain coincides
Direct Feminization/Demasculinization with the establishment of adult sexual
behaviours and is guided by hormone secretion.
Along with the immediate effects on For example, the Sexually Dimorphic Nucleus
reproductive success, i.e., eggshell of the Preoptic Area (SDN-POA) is a region of
thinning/breakage and abortion/premature birth, the hypothalamus that, in rats, develops in a
DDT exposure can result in feminization and span of a few days. The size of the SDN-POA is
demasculinization of the offspring. One example two or more times larger in males than females.
comes from the southern coast of California Once a female is born, the size of the SDN-POA
where the poor breeding success of brown becomes fixed. Perturbations of hormone
pelicans, double-crested cormorants, and other signals between day 16 to 22 of prenatal
birds resulted from a reduced number of adult development can alter the size of the SDN-POA,
males (a highly skewed sex ratio: 3.8 females the future frequency of lordosis (mounting
for each male), and female-female pairing behaviour), and luteinizing hormone (LH)
(Gress et al., 1973; Anderson et al., 1975). In a
20
concentrations (Rhees et al., 1997; Rhees et al., ventromedial nucleus. Thus, masculization can
1990a, 1990b; Davis et al., 1995). be affected by estrogen or estrogen agonists,
such as o,p‘-DDT or DES (Tarttelin and Gorski,
In humans, the preoptic area has a window of
1988; Dohler et al., 1984). In addition, the
development associated with the LH-releasing
estrogen receptor can be blocked by anti-
hormones (Kandel et al., 1995) that is believed
estrogen compounds such as tamoxifen, which
to open near the ending of the first trimester
is used in cancer treatments. If tamoxifen or
with changes in size evident early in postnatal
another anti-estrogen is present during
development (Kaplan et al., 1976).
development, estrogen hormone messages are
The SDN-POA is one of the regions of the blocked, simulating an absence of estrogen and
hypothalamus whose neurons manufacture and the presence of the female state (Vancutsem and
secrete luteinizing-releasing hormone and Roessler, 1997).
gonadotropin-releasing hormone. These
Since this process is mediated through estrogen-
releasing hormones travel to the pituitary where
receptor processes, concern is raised that the
they signal the release of LH or follicle
presence of estrogen mimics during these early
stimulating hormone (FSH). The nuclei
stages of development can masculinize and
differentiate in late fetal life and their form
defeminize female brain function and behaviour.
(morphology) is determined by the ratio of
Laboratory experiments underscore the
estrogen to testosterone concentrations in the
exquisite sensitivity of developing embryos to
fetus during a critical moment during
low doses of estrogen, testosterone, and
development (Dohler and Jarzab, 1992).
chemicals that mimic or otherwise interfere with
Another developmental window opened during them. For example, masculinization and
this same period involves the ventromedial defeminization of female mice has been reported
nucleus of the hypothalamus. This region is when these fetuses are developing beside two
associated with the expression of sexual male pups in utero (vom Saal et al., 1992). The
behaviour. In rats, exposure to estrogen through source of testosterone in this in utero example is
aromatase activity on testosterone establishes the natural diffusion that occurs across the
male mating behaviours (Kandel et al., 1995). embryonic membranes that enclose each embryo
Female rats exposed to testosterone during this and is estimated to be parts per trillion in
period became more aggressive and physical concentration.
during bouts of play.
Studies of the population of western gulls nesting
Such behavioural differences are the result of a in the Channel Islands, off the coast of southern
very unusual hormone triggering system. California and herring gulls from the Laurentian
Estrogen is typically thought of as a feminizing Great Lakes in the 1960s and 1970s, showed a
hormone and testosterone as masculinizing in its high incidence of supernormal clutches and
effects. This is true regarding the development female-female pairing (Hunt and Hunt, 1977;
of the reproductive tract and expression of Shugart, 1980). This is an abnormal phenomenon
secondary sexual characteristics. However, since gulls are long-lived monogamous species
during development of certain regions of the that usually lay 2 or 3 eggs every year. Further
brain, estrogen acts to masculinize. During the studies revealed that these supernormal clutches
were a result of multiple females sharing the same
early stages, free estrogen occurs at very low
breeding space. Fry and co-workers studying
concentrations as a protective measure to limit
female-female pairing of western gulls, California
estrogen-mediated pathways during gulls, and herring gulls concluded that the
development. However, testosterone secreted by increased number of females and decreased
the developing testis disperses readily population of the gulls could be a reflection of the
throughout the fetus, enters cells, and is fact that the majority of male gulls in 1970s were
converted to estrogen by aromatase, an enzyme feminized and incapable of reproduction and also
specific for this purpose. Aromatase is produced very few eggs in supernormal clutches were fertile.
in select cells in the hypothalamus, so synthesis Wingfield et al. (1982) and Hunt et al. (1984)
of estrogen is extremely localized. But it is this reported that there are no significant hormonal or
estrogen that masculinizes the preoptic area and behavioural differences between females paired
21
with females and those paired with males. pass messages in the neural tissues.
However, embryonic feminization of males may
result in suppression of sexual behaviour and self- Neural Effects of Pesticides
exclusion from the breeding colonies.
A majority of the pesticides used for vector
control achieve their results through alterations
Effects on the Nervous System in the nervous system of pest and non-target
species. These pesticides include DDT,
Overview of the Nervous System methoxychlor, the synthetic pyrethroids,
carbamates, and organophosphates (Ware, 1994;
The nervous system functions by the Narahashi, 1992; Casida et al., 1983). While
transmission of electrical impulses along the these chemicals may cause mortality in the pest
nerve cells (neurons) that comprise it. As the with no visible neural damage to non-target
neurons connect during development, synapses species, other more subtle developmental effects
or junctions are formed where two neurons have been recently reported. For example, DDT,
connect. Neurotransmitting chemicals convey bioallethrin, and deltamethrin can shift the
signals across these junctions. Receptors for the proportion of the two receptor types mentioned
neurotransmitters form and become permanently previously, resulting in conditions that can lead
attached to the surface of the nerve cell at the to hyperactivity of the nerves. When mice were
synapse. These receptors become the site of exposed to DDT or deltamethrin on the tenth
attachment of the neurotransmitter messenger day after birth, permanent changes were seen,
released by the neighboring neuron that is which persisted in the adult four months later
passing its electrical message. When a sufficient (Eriksson, 1992; Eriksson et al., 1992). Table II-
number of receptors in the synapse have 4 also outlines other effects from laboratory
neurotransmitters attached, a threshold is studies of [DDT and] deltamethrin.
reached and the neuron receiving these
transmitters begins conveying its own electrical Pesticides, including those commonly used in
signal to the next neuron beyond it. vector-control programs, have not been
Acetylcholine is a common form of routinely screened for alterations in synaptic
neurotransmitting chemical in nerve tissues. receptor development. Studies with mice and
There are two types of receptors that respond to rats further document gross anatomical,
this chemical. One type holds the morphological, and functional changes in the
neurotransmitters longer than the others, thereby brain with exposure in utero. They also show
influencing how signals are passed. The blend linkages between such changes and other end
of the two types establishes the sensitivity of the points, such as behaviour. These effects involve
nerve; if the balance is not correct, the nerve brain structure and as such, direct effects on
may be activated or fired too easily, providing humans are difficult to assess.
hypersensitivity, or may require more time to
22
Table II-4: Neurological Effects from Neonates’ Exposure to Low Doses of Pesticides
Species Exposure Response Effect Reference
mice DDT Altered proportions of receptor increases Eriksson,
neonate 0.5 mg/kg types sensitivity of 1992
Day 10 (15 ppt in brain) Spontaneous behaviour changed nerves
age 10 days when adults (habituation) (irreversible)
mice Deltamethrin Altered proportions of receptor increases Eriksson,
neonate 0.5 mg/kg types sensitivity of 1992
Day 10 (15 ppt in brain) Spontaneous behaviour changed nerves
age 10 days when adults (habituation) (irreversible)
rats Deltamethrin Changes in weight and enzyme changes in Husain et
adult 7.0 mg/kg activity among regions of brain behaviour al., 1996
for 15 days Increased spontaneous motor
activity and aggressive behaviour
Decrease in maze learning
rats Deltamethrin. Brain & body weight decreased neurogenesis Patro et al.,
neonates 0.7 mg/kg Neural development delayed and final brain 1997
day 9 - 13 for 5 days including proliferation and anatomy
migration altered
Reduced blood flow in brain
Nerve cells also establish and pass electrical switches that is responsible for neural
impulses by manipulating the balance of two functioning.
chemicals – sodium and potassium – inside the
Pesticides can block the receptors or destroy the
cell. DDT and synthetic pyrethroids interfere
enzymes whose job it is to remove
with and slow the actions of the cellular pumps
neurotransmitters. For example,
that change levels of sodium and potassium,
organophosphate and carbamate pesticides can
thereby slowing the frequency with which
destroy the enzyme acetylcholinesterase that is
neurons transmit electrical signals.
responsible for destroying the neurotransmitting
Other pesticides alter additional facets of the chemical acetylcholine. Destroying this enzyme
communication process in the nervous system. leads to uncontrolled discharges. When a large
When an electrical nerve impulse reaches the number of neurons are so influenced, classic
end of a nerve, specialized vesicles release pesticide poisoning effects are experienced
neurotransmitter molecules (such as including twitching, tingling sensations,
acetylcholine, noradrenalin, dopamine, tremors, convulsions, seizures, and possibly
serotonin, or gamma-aminobutyric acid) into the even death.
synaptic junction that connects two neurons.
Nervous systems vary within an individual,
The neurotransmitter molecules diffuse across
between individuals of the same species, and
the gap and bind to specific receptors in the
between species. Neurons in regions of the brain
membrane of the next link in the neural
have subtle differences in the numbers of
pathway. After the neurotransmitters do their
receptors in the synapses, the types of
jobs, they are chemically destroyed by enzymes.
neurotransmitters used, and the methods used to
This resets the receptor for reception of another
restore synaptic conditions. Neuromuscular
wave of neurotransmitters. It is this sequential
junctions, the neural connections that carry
passing of electrical discharges by chemical
signals to muscles, differ from the typical
23
synapses in the brain and thus have different and thymus. The successful development of the
susceptibilities to neurotoxic chemicals. immune system requires that the primordial cells
Susceptibility also differs among species and is multiply, migrate, and become established
more related to increased complexity and throughout the body so that they can provide the
alternative methods by which an organism can wide diversity of cell types that comprise the
degrade or sequester nerve poisons. immune system.
Granulocytes (neutrophils, eosinophils,
Effects on the Immune System basophils) comprise one class of these highly
specialized immunological cells. They are
Overview of the Immune System produced in the bone marrow and released
during inflammation. Neutrophils and
The immune system provides the primary eosinophils actually engulf, in a process called
defense against invasions by foreign materials phagocytosis, foreign material and debris which
such as microbes and parasites. It also protects are then digested inside the cell using
the body from aberrant or damaged cells, such specialized enzymes. Basophils also release
as tumors. The immune system is a complex histamines that increase inflammation at the site
assemblage of cells and organs (spleen, lymph of the infection; this acts as a beacon to call in
nodes, thymus, bone marrow) that have highly more granulocytes to the site.
specific and, to a degree, overlapping functions.
No single type of cell is sufficient, however, to Lymphocytes are a second major subdivision of
provide all of the defenses necessary for the the immune system, and are composed of B- and
wide variety of possible assaults. The immune T-lymphocytes. There are approximately two
system is tied to the endocrine and nervous trillion B-lymphocytes in the body. Their
systems, both in its development during progenitor cells are located in bone marrow and
gestation and early postnatal life, as well as are the source of all B-lymphocytes an
during its operation throughout life. Many of individual will ever have. Each B-lymphocyte is
these interconnections are only now being capable of manufacturing a unique and highly
elaborated. specific antibody that is used to bind to antigens
(pathogens and other foreign matter) found
An abundance of literature describes immune outside cells. One B-lymphocyte can release as
suppression from exposure to pesticides many as 3,000 antibodies per second. These
(reviewed by Repetto and Baliga, 1996). Much antibodies drift in body fluids and when they
of the attention has been focused on agricultural meet the antigen, they bind and facilitate its
applications of organochlorines, rapid ingestion by the white blood cells
organophosphates, carbamates, and (phagocytes). Since the antibodies passively
thiocarbamates and only recently have drift throughout the body, it is necessary to
pesticides commonly used in vector-control produce them in vast quantities. Millions of
programs been studied. Technical grade DDT lymphocytes producing antibodies may seem
and the synthetic pyrethroids cypermethrin, like a formidable defense, however, because
deltamethrin, and permethrin, have effects on each B-lymphocyte remains dedicated to
the immune systems of mice, rats, rabbits and producing an antibody specific to a single
goats (Table II-5). antigenic particle, a large number of such cells
is required in order to maintain an adequate
repertoire or ―library‖ to fight a broad range of
Immune System Development infections.
The different cell types that make up the T-lymphocytes are another critical component
immune system arise from primordial stem cells of the immune system and arise from the thymus
that form early in development. These cells gland. During the 11th day of development in the
differentiate into a variety of more specialized mouse or the 8th week in the human, stem cells
cells that ultimately populate the bone marrow
in the bone marrow migrate to the thymus where
24
they differentiate into progenitor cells that give incorporated into lymphocyte ‗memory‘ from
rise to mature T-lymphocytes. These cells which future invasions can be quickly identified
migrate from the thymus early in life and and even quicker future responses provided. Not
circulate in blood, acting as coordinators of every B-lymphocyte can respond in this fashion
immune responses (T-helper lymphocytes) or to each specific foreign molecule. When
killers of virus-infected cells (T-cytotoxic created, they acquire a limited array of ―non-
lymphocytes and Natural Killer [NK] cells). self‖ recognition abilities and thus when a
Since the thymus becomes smaller as an foreign molecule enters the system only a small
individual matures, the thymus of a mature component of the total complement of
individual can be removed with no visible lymphocytes can identify it as foreign and
detrimental effects. However, if the thymus is respond.
removed or disturbed during development, this
Immunization programs utilize this recognition
line of defense can be adversely affected.
ability by introducing benign or ―killed‖ parts of
Thymus weight, an indicator of the health of this
the pathogen to ―teach‖ the immune system how
organ, decreases when exposed to DDT or
to recognize a specific pathogen. The
cypermethrin during gestation or early
appropriate B-lymphocytes locate and recognize
development (Santoni et al., 1997; Queiroz,
these as a foreign threat, which triggers the
1993).
rapid cellular multiplication of these specific
In contrast to B-lymphocytes, which work lymphocytes. When immunity is acquired in this
outside cells, T-lymphocytes specialize in fashion, a large population of primed B-
clearing an infection that is already established lymphocytes with a ‗memory‘ are the sentinels
within the cells of the body. T-helper cells that offer the first critical response in an
provide an important function in coordinating eventual exposure situation.
the various components of the immune system
The response component of the immune system
through secretions of cytokines, such as
is the defense against invasions of pathogens
interleukins, interferons, and colony-stimulating
and includes many cell types that are specialists
factors. The cytokines are chemical messengers
in defense against specific kinds of foreign
through which the lymphocytes coordinate the
bodies like bacteria, viruses, and parasites in
activity of other cells in the immune system. T-
body fluids; target cells that have been invaded
helpers also destroy cells by perforating the cell
by pathogens; and debris associated with
surface. NK cells play a critical role in
infections and wounds. Hormonal response
destroying tumor cells and for this reason the
involves the production of antibodies which
immune system plays a critical role in the
come in contact with the antigens, bind, and
prevention of spontaneous cell proliferations
cause them to precipitate, dissolve, or to stick
that may lead to cancer.
together forming agglutinated masses. Then
phagocytic cells destroy them.
Pathogen Recognition and Response ―Cell-mediated‖ response relies on the activity
of specific cell types to aid in locating antigens,
The immune process involves two basic
binding to them, and ingesting viruses and
activities: recognition of foreign material and
bacteria or encapsulating parasitic organisms.
response to its presence. Recognition hinges on
Furthermore, some of the cell types in the
lymphocytes‘ ability to detect subtle differences
immune system serve coordinating functions as
between ―self cells‖ and foreign material.
they move to sites of infection and release
Furthermore, differences among foreign
homing chemicals that call in masses of white
materials can be identified and highly specific
blood cells.
responses can be directed against them. For
example, lymphocytes can recognize as A lymphocyte has its own small repertoire of
―different‖ a long protein in which just a single antigens it can recognize. An effective immune
amino acid has changed. This identification is system relies on a very large population of these
25
cells to increase the likelihood of recognition. Effects of Pesticides on the Immune
When a particular lymphocyte finds an antigen System
invader, it springs into intense activity since it
must be responsible for producing both the Pesticides have been demonstrated to lead to
chemical defense as well as more lymphocytes immune suppression (Repetto and Baliga,
to help with the task. That translates into a few 1996). Outcomes include detectable changes in
specific cells giving rise to a lineage of antibody production, lymphocyte proliferation,
thousands of clones designed for this one phagocytosis rates and white blood cell counts,
purpose. It can take about five days for the cells as well as increases in the time it takes to
to undergo these divisions. Disease resistance respond to infections. Much of the attention has
depends on the ability of the body to both mount focused on organophosphates, carbamates, and
an adequate defense relying on the two trillion organochlorine pesticides. A pattern of effects
B-lymphocytes and to quickly mobilize a small has been documented for DDT and such
subset of appropriate cells to combat a particular synthetic pyrethroids as cypermethrin,
infectious assault. The rates of cell divisions are deltamethrin, and permethrin (Table II-5). The
key to quickly stemming the assault especially if specific immunological effects include changes
to: 1) lymphoproliferation (production of
the pathogen itself is dividing during its attack.
lymphocytes), 2) the humoral response rate, 3)
thymus weight, and 4) overall system
performance.
Table II-5: Reports of Effects of DDT, Cypermethrin, Deltamethrin and Permethrin on the
Immune System of Mice, Rats, Rabbits, and Goats
Species Exposure Response Effect Reference
mice DDT Humoral response not altered h Banerjee et al.,
20, 50, 100 ppm (antibody titer and plaque- 1997
4 weeks forming cells)
Humoral response decreased
when animal stressed (handling
or temperature)
mice DDT Humoral response decreased c.m. Banerjee et al.,
20, 50, 100 ppm Plaque-forming cells decreased 1986
3-12 weeks
rats DDT/DDE/DDD Humoral response suppressed h Banerjee et al.,
200 ppm 1996
6 weeks Cell-mediated response c.m.
suppressed
mice DDT Humoral response decreased h Banerjee, 1987a
20, 50, 100 ppm
3-12 weeks Plaque-forming cells decreased c.m.
rats DDT Humoral response decreased h Banerjee, 1986
20, 50, 100 ppm
8-22 weeks Lymphocyte mobility altered c.m.
rats DDT Humoral response decreased in h Banerjee, 1987b
20, 50, 100 ppm highest dose
8-22 weeks Immunoglobulin concentration
decreased with tetanus toxoid
challenge
Decline in migration inhibition c.m.
26
Species Exposure Response Effect Reference
factors
rats DDT At 50 or 100 ppm a 3% protein h Banerjee et al.,
20, 50, 100 ppm diet leads to suppression of 1995
4 weeks humoral and cell-mediated c.m.
responses
mice DDT Lymphoproliferative response to m Rehana and
0.0316, 0.316, 3.16 LPS decreased at highest doses Rao, 1992
mg/kg/day T-Cell plaque-forming decreased
for 6 months at highest dose. c.m.
mice DDT Lymphoproliferative response m Rehana and
(offspring 0.0316, 0.316, 3.16 decreased which continued over Rao, 1992
of exposed mg/kg/day time
mothers) for 6 months Plaque-forming cells decreased c.m.
in two highest
mice Cypermethrin Lymphoproliferative response m Stelzer and
-5 -5
1x10 M to 5x10 M decreased in both T- and B- Dordon, 1984
lymphocytes
mice Cypermethrin Tuberculin Skin Test decreased c.m. Tamang et al.,
50 mg/kg/day response 1988
for 26 days
rats Cypermethrin Dose dependent decrease in h Varshneya et al.,
5, 10, 20, 40 mg/kg/day delayed hypersensitivity 1992
for 90 days Lower leukocyte count in highest
dose
Depression in cellular response
rats Cypermethrin No effects seen _ Madsen et al.,
4, 8, 12 mg/kg/day 1996
for 28 days
rats Cypermethrin Peripheral NK-cells increased c.m. Santoni et al.,
(prenatal 50 mg/kg/day Antibody-dependent cytotoxicity h 1997
exposure) for 10 days over Day 7 to increased
Day 16 of gestation Lymphocytes: more in plasma,
fewer in thymus gland
rats Cypermethrin Two highest doses: decreased Desi et al., 1986
1/40, 1/20, 1/10 LD50 Complement Binding and hl
Agglutination Test
Plaque-formation in spleen cells c.m.
rabbits Cypermethrin Dose dependent reduction in: Desi et al., 1986
1/40, 1/20, 1/10 LD50 Agglutination test h
Complement Binding h
Tuberculin Skin Test c.m.
goats Cypermethrin Tuberculin Skin Test decreased c.m. Tamang et al.,
41.6 mg/kg/day response 1988
for 30 days Plaque-forming response h
decreased
mice Permethrin Lymphoproliferative response m Stelzer and
-5 -5
1x10 M to 5x10 M decreased in both T- and B- Gordon, 1984
lymphocytes
mice Permethrin Lymphoproliferative response Blaylock et al.,
0.4, 0.04, 0.004 mg/kg not altered 1995
for 10 days Mixed lymphocyte response
(1%, 0.1%, 0.01% LD50) reduced c.m.
Lysis activity decreased c.m.
NK cell activity to tumor cells
27
Species Exposure Response Effect Reference
decreased c.m.
mice Deltamethrin Significant decreases: Lukowicz-
6 mg/kg for 84 days Agglutination Test h Ratajczak and
or Hemagglutinin Test h Krechniak, 1992
15 mg/kg for 14 days Plaque-forming response c.m.
mice Deltamethrin Bone marrow stem cells colony Queiroz, 1993
5 mg/kg for 3 days formation increased
Thymus weight decreased
rats Deltamethrin Highest doses: significant c.m. Madsen et al.,
1, 5, 10 mg/kg/day enhancements of 1996
for 28 days SRBC-Plaque-forming cells
and NK-cell activity
Significant increase in lymph
node weight; reduction in thymus
weight
h = humoral; c.m. = cell mediated; m = mitogen
Effect on Lymphocyte Function decreased lymphoproliferation. Furthermore, by
12 weeks of age the rate continued to decline
DDT, cypermethrin, and permethrin decrease (Rehana and Rao, 1992).
the division rates of T- and B-lymphocytes in
laboratory cultures, suggesting a functional Effect on Humoral Response
impairment of these cells (Rehana and Rao,
1992; Stelzer and Gordon, 1984; Blaylock et al., There have been few studies involving exposure
1995). Additional effects were identified from to DDT and effects on the immune system.
exposure of these lymphocytes to pesticides. For Work on adult mice and rats (Banerjee et al.,
example, the rates at which foreign bodies were 1986; Banerjee, 1987) indicates that exposure to
dissolved decreased when T-lymphocytes were DDT leads to the suppression of primary and
exposed to permethrin (Blaylock et al., 1995). It secondary humoral responses. When mice were
is not known whether a decreased exposed to 100 ppm there were significant
lymphoproliferative rate was sufficient to alterations in antibody titers and the numbers of
account for this decrease or if additional effects plaque-forming cells. This response was
of permethrin resulted in this decline. Likewise, affected by the duration of the exposure, thus
NK cells also showed decreased cytolytic suggesting a threshold level of exposure is
activity (Blaylock et al., 1995). It is not known necessary for these observed effects. Banerjee
if this effect was due to a suppressed rate of (1987) hypothesized that the reductions in
early mitotic divisions or is a manifestation of a humoral response are mediated through effects
functional impairment of these or other cells of on B-lymphocytes.
the immune system. Rats also showed reductions in humoral
Mice exposed to DDT in utero and during responses when exposed to DDT (Banerjee et
lactation had a decrease in the rate of al., 1986). Exposure to 100 ppm for 18-22
lymphoproliferation (as high as 37%), weeks or to 50 ppm for 22 weeks led to a
regardless of the pesticide concentrations significant decrease in humoral response. This
administered in the study (Rehana and Rao, observation coincides with the effects seen in
1992). These effects are transgenerational. mice where duration of exposure suggests a
Female mice were exposed over six months and threshold level for effects. Banerjee further
mated to control males. The offspring were noted that rats exposed to either 50 or 100 ppm
divided into two groups, one receiving DDT and and later immunized with a tetanus toxoid had a
the other unexposed. All these offspring showed decrease in mobility of the lymphocytes,
28
possibly further reducing the immune defenses. effect this may have had on the performance or
Additional work is necessary to test the fate of the released lymphocytes is not known
significance of the threshold effect seen in the since such tests were not conducted.
Banerjee studies and to determine if lower dose
exposures over longer periods of time will Effect on Overall Immune System
provide comparable reductions in humoral Performance
responses. Furthermore, the ramifications of a
Observing individual components of the
change in mobility in the B-lymphocytes and the
immune system may provide benchmarks of
degree that this may contribute to potential
effects. However, it becomes difficult to predict
health effects are unknown.
if these are sufficient to lead to undesirable
Cypermethrin and deltamethrin have been health outcomes. The Tuberculin Test can be
reported to lead to a decreased ability to bind useful in assessing these overall outcomes. In
antigens. This may be related to a decreased this test, an organism such as mycobacterium is
amount of antibody production (Desi et al., inoculated with an antigen in a sufficient
1986; Lukowicz-Ratajczak and Krechniak, quantity to insure sensitization of all
1992). Desi et al. (1986) describe reductions in components of the immune system. Memory
humoral response in rabbits dosed with 1/40, cells are created and distributed in the body and
1/20, or 1/10 proportion of the LD50 value for antibodies are primed for production. When a
cypermethrin, which they determined to be small amount of this antigen is placed in the
3,000 mg/kg. The response was observed within skin of the animal, the immune system springs
one week of the initial exposure and was dose into activity and all facets of this response
dependent, with the two higher concentrations contribute to an observable and measurable
demonstrating significant reductions in antibody swelling and inflammation at the site of
responses. Lukowicz-Ratajczak and Krechniak injection. The resulting size and amount of
(1992) observed similar results when they swelling, the color of the skin, and duration of
exposed mice to a concentration of deltamethrin the reaction are all indicators of the health of the
of either 6 mg/kg or 15 mg/kg. Furthermore, immune system. In one experiment for example,
plaque-forming cells were also reduced in cypermethrin exposure prior to sensitization
number, which is another indication of a increased the reaction time and decreased the
diminished humoral response. intensity of the immune response (Tamang et
al., 1988). This study did not, however, identify
Effects on Thymus Weight what component of the system was diminished.
As noted previously, perturbations early in
Significance of Immune Suppression from
development can have graver consequences for
lymphocyte populations than later in life. Since Pesticide Exposure
the T-lymphocytes are distributed throughout Determining the significance of immune
the body after leaving the thymus, this organ can suppression from exposure to pesticides used in
be removed in adults with minimal effect to the vector-control programs is not a simple
immune system performance. However, if the exposure problem. The carefully controlled
excision or perturbation occurs prior to the experiments where mice or rats are dosed in
migration, significant effects are observable precise amounts provide only a glimpse of the
upon pathogen challenges, thus making the potential scope of the problem. For example,
effects of pesticides during this stage of great Banerjee and colleagues demonstrated that
importance. Santoni et al. (1997) reported that pesticide exposure in conjunction with
rats prenatally exposed to cypermethrin during environmental stressors can increase the
days 7 to 16 had a reduced thymus weight and magnitude of observed effects. More
decreased numbers of T-lymphocytes in the specifically, diets deficient in protein
gland. There was an increased lymphocyte count contributed to a reduction in immune
in the plasma, which may reflect an accelerated responsiveness in rats previously exposed to
release of lymphocytes from the thymus. What pesticides (Banerjee et al., 1995). Rats that had
29
been exposed to 50 or 100 ppm DDT for 4 may be the kinds of effects observed by Rehana
weeks and then maintained on a low protein diet and Rao (1992) and identified as permanent
(3%) had a depressed humoral and cell-mediated reductions in immune competency.
response when challenged with an antigen. Rats
Coincident with immune suppression in general
consuming more protein-rich diets (12-20%) did
are increased frequencies of infection and
not demonstrate this immunosuppressive effect.
cancer (Descotes et al., 1995). For example,
Banerjee et al. (1997) also demonstrated Kaskhedikar and colleagues (1996) exposed
reductions in humoral response associated with adult mice to graded doses (0.0078, 0.03125,
stress (immune system performance is known to 0.125, or 0.5 ml/kg) of malathion in their food
be tightly intertwined with endocrine and over the course of five, ten, or fifteen
nervous system function); mice exposed to 20, consecutive days, and then infected them with
50, or 100 ppm DDT for 4 weeks did not show a 500 viable eggs of a nematode. Twenty-one days
reduction in the number or response of plaque- later, the intestines were examined for live
forming cells when challenged with sheep red nematodes.
blood cells (SRBC). When these animals were
The larger the dose of malathion and the longer
handled or held, however, they showed dose-
its duration, the larger the number of surviving
dependent declines. This raises concerns that
worms (Table II-6), signaling a weakened
these subtle shifts may lead to adverse health
immune system response. The researchers did
effects especially to sensitive components of the
not extend their study to determine possible
population, such as the very young, developing
ramifications of higher parasite loadings on
individuals, or the elderly.
these mice. However, it is reasonable to suspect
Banerjee et al. (1996) also observed that DDE that the stress, lost energy, and physiological
and DDD surpass DDT in their ability to imbalance caused by both the parasites and the
suppress the humoral response in rats. DDE damage they may do to the intestinal lining are a
accumulates rapidly and readily in the body, and detrimental health effect and may affect the
is passed freely in breast milk to nursing animal‘s survival and reproductive success. This
offspring. It is not known what exposures during also represents a model for pathogens and thus
fetal and postnatal periods of life can do during host resistance to other infectious agents may be
the critical period when the immune system is diminished as well.
being activated and primed. For instance, these
Table II-6 Parasites Reported in Mice Exposed to Malathion and Subsequently Infected
with Known Numbers of Parasites (Kaskhedikar et al., 1996)
Duration of Exposure 5 5 10 10 15 15
to Malathion (Days)
Dose of Malathion
ml/kg body weight WB PWB WB PWB WB PWB
0.0078125 70 14.0 91* 18.2 102* 20.4
0.03125 85* 19.0 108* 21.6 122** 24.4
0.125 102* 20.4 130** 26.0 148** 29.6
0.500 122* 24.4 142** 28.4 160** 32.0
WB= Worm Burden; PWB = percent of worm burden based on the 500 initially infected; * = statistically significant
difference; **=highly significant result.
30
DDT and Cancer have identified a wide range of associations:
early menarche, nulliparity, late age of first
The U.S. EPA has identified DDT as a probable
birth, onset of menopause, oral contraception,
human carcinogen (ATSDR, 1994a) based on
estrogen replacement therapy, ionizing
lab studies; liver and lung tumors found in mice
radiation, and fat content. These factors account
and rats were a result of chronic exposures
for about 30% of breast cancers, leaving the
(Kashyap et al., 1977; Terracini et al., 1973;
remaining 70% of the breast cancers
Thorpe and Walker, 1973; Tomatis et al., 1974;
unaccounted for.
Rossi et al., 1977). Human epidemiological data
do not provide clear evidence of the Environmental factors, including synthetic
carcinogenicity of DDT to humans (Houghton chemicals, are thought to be involved, in part, in
and Ritter, 1995). the unaccounted breast cancers. Proponents of
this hypothesis see further support in a report by
On the whole, human studies have been
the U.S. National Cancer Institute‘s
exceedingly rare, being restricted to exposure
Surveillance, Epidemiology and End Results
during the manufacture or application of DDT,
Program that described newly diagnosed breast
with reports that cancer incidences were not
cancer rates increasing 1% per year between
significantly different from control groups. Part
1950 and 1979, and 3% between 1980 and 1984.
of the difficulty associated with these studies
When analyzed by the kind of tumor based on
relates to the determination of exposure history,
the receptor content, estrogen-receptor-negative
effects of mixtures, and sample sizes.
tumors rose 22-27% between the mid-1970s and
Furthermore, the latency period for the
mid-1980s, while the number of estrogen-
development of cancer is estimated to be from
receptor-positive tumors increased an average of
10 to 20 years, making direct causal links
131% (Glass and Hoover, 1990).
difficult to establish (Dewailly, Ayotte, and
Dodin, 1997). This is particularly important if Pujol and colleagues (Pujol et al., 1994)
causal agents such as DDT act in such a way as analyzed 11,195 samples of breast cancer
to predispose susceptibility during very early tumors collected between 1973 and 1992 and
life and effects are expressed long after the found that the quantity of estrogen receptors has
agent disappears from the tissue. steadily increased to levels about four times
higher over the 20 year period. They suspect
DDT and Breast Cancer that this change is a reflection of hormonal
events that influence breast cancer genesis and
There has been considerable recent discussion
growth, and not differences in techniques or
of a possible link between DDT and the
screening programs. Later age at first
occurrence of breast cancer, although there
pregnancy, early age at menarche, and
remains considerable scientific uncertainty and
nulliparity have also been associated with
debate (Houghton and Ritter, 1995). The case
estrogen-receptor-positive tumors. However,
for concern that DDT is associated with
these authors hypothesize that the increase in
increased cancer in humans involves a series of
the numbers of estrogen receptor-positive
observations relating to: 1) known causes of
tumors could be associated with induction by
breast cancers; 2) changes in frequency of
estrogen or estrogen-agonists, leading to the
cancer in the population; 3) shifts in types of
development of estrogen receptor-positive
breast cancers seen; and, 4) patterns of chemical
cancers (Pujol et al., 1994).
contaminant levels in tumor tissue.
In another study that measured organochlorine
Breast cancer due to mutations of genes only
concentration in relation to the estrogen-
accounts for about 10% of breast cancers in the
receptor status of the tumor, it was found that
United States (Pollner, 1993), leaving 90% of
estrogen-receptor-positive tumors had
the cases for non-genetic causes.
significantly higher concentrations of DDE than
Epidemiological studies have tried to identify
did the controls (Dewailly et al., 1994). This
other known risk factors for breast cancer and
highlights the need to view cancers not as a
31
single endpoint but as a class of outcomes of breast cancer in the same ―trans-generational‖
involving different cells and tissues, promoters, manner as they influence other health endpoints,
and developmental pathways. When estrogen then studies of adult concentrations can provide
receptor-positive breast cancer tumors become only limited insight. To truly establish whether
associated with elevated concentrations of there is a link between DDT (and other synthetic
chemicals such as DDT or DDE, it is reasonable chemicals) and the occurrence of breast cancer,
to suggest a causal link (Pujol et al., 1994). it is essential to determine if breast cancer
Furthermore, this linkage extends to endocrine- victims were exposed to such chemicals in the
disrupting chemicals since hormonal agonists or womb or during early childhood.
antagonists have the potential to mimic the
behaviour of natural hormones that may be
involved in pathways that lead to cancer. DDT
Summary
is a likely candidate for consideration as a Concerns over DDT‘s carcinogenicity,
causal agent for breast cancer since one isomer bioaccumulation, persistence, hazards to
is known to be an estrogen agonist (o,p‘-DDT) wildlife and other chronic effects have led to its
and can therefore act as a cancer promoter. At ban in 49 countries and restriction in 29 more.
present, there are no data to support these The weight of scientific evidence about its
concerns. negative health and environmental effects
continues to mount. Many of these effects,
When comparing women who developed breast particularly endocrine disruption, were poorly
cancer with controls, Wolfe and associates studied when the WHO Study Group on Vector
found higher concentrations of DDT and DDE Control for Malaria and other mosquito-borne
in women who had developed breast cancer, diseases made its recommendations in 1993 to
though only DDE concentrations were continue the use of DDT. At that time, there
statistically significant. More recently, Hunter et were insufficient toxicological data to suggest
al. (1997) report that with more careful that indoor spraying might be harmful to
screening of participants and an increase in the humans. This is no longer the case, as this
sample size, no association was detected with section has shown and the following one further
DDE and breast cancer incidence. Such studies illustrates.
involving associations of breast cancer and
serum pesticide levels rely on measurement in In its 1993 decision, the Study Group did not
adulthood, but since breast cancer is a disease take the well-documented effects of DDT use on
with a long initial period of development, the wildlife and conservation into consideration.
role of a chemical such as DDT could be Today those effects are better understood and
obscured. Plasma concentrations can vary, more far-reaching than previously known. Given
especially when women are breast feeding. that many biological processes are conserved
Moreover, the possible role of these chemicals across species, DDT‘s known and suspected
in diseases like breast cancer has not been effects on wildlife and laboratory animals
assessed for developmental effects of exposures should be considered as probable effects on
in utero, lactational exposures during early humans.
development, and exposures later in life. These Concerns for the subtle endocrine disrupting
may well promote such diseases, but when and/or developmental effects are not limited to
associations are sought, current concentrations DDT and its metabolites. Recent research
are not representative of exposure history. This highlights the fact that biologically active
is not meant to argue that DDT does or does not chemicals can have unanticipated effects, some
cause cancer, only that the designs of of which can lead to an irreversible cascade of
experiments published to date do not target or events that alters the future functioning of
consider developmental consequences in their tissues and organs. The few synthetic
assessments of association. If synthetic pyrethroids studied demonstrate such effects to
chemicals that mimic, block, or otherwise neural development, neural performance, and
influence hormones play a role in the occurrence
32
expressed behaviour, as well as forms of body weight.) Indeed, research in Mexico and
immune suppression. Although these pesticides elsewhere has revealed measured concentrations
may lack the persistence and ability to of DDE in humans that exceed health
bioaccumulate seen in DDT, chronic, low dose authorities‘ guidelines for acceptable exposure
exposures may lead to subtle developmental (Torres-Arreola et al., 1998).
effects. A more rigorous research program is
The concentrations of DDT in breast milk in
necessary to identify such effects and to
Table I-5 illustrate the variability of exposure,
determine their significance.
long-distance transport, and long half-life. There
are reports that low-birth-weight babies and
III. EXPOSURE AND ITS premature babies had higher levels of DDE in
their blood compared to normal-weight and full-
IMPLICATIONS
term babies (O‘Leary et al., 1970). Also, higher
levels of DDT and its metabolites were found in
Levels of DDT in Humans the breast milk of women who had the
It is reported that worldwide levels of DDT and premature babies (Berkowitz et al., 1996).
its degradation products have been slowly Evidence has also shown that elevated
declining over the past 25 years as countries concentrations of DDE are associated with
have banned its use. In humans and animals, reduced lactation by human mothers (Gladen
DDT levels have declined from a global average and Rogan, 1995). Even after dramatic
of 12 ppm to below 7 ppm (IEM on POPs, reductions in DDT use world-wide, breast
Annex II). These levels vary widely however, feeding women in the most remote locales today
depending on the location and various are unintentionally feeding their infants
characteristics of sub-populations. For instance, concentrations of a known endocrine disruptor
the concentrations of p,p‘-DDE in breast milk in at a critical stage of their offspring‘s
women in Zimbabwe are 25 times higher than development (Tables III-1 & III-2). DDT levels
American women (Table I-5). Even within in the milk of Inuit women in the Arctic are
regional populations concentrations vary five-fold higher than those of women living in
dramatically. Sampling of breast milk in southern Canada, reflecting their greater
Veracruz, Mexico in 1994 and 1995 showed consumption of traditional foods which are high
concentrations ranging from 0.99 to 26.9 mg per on the food chain. A 5-kg Inuit infant
kg of fat. Infants drinking this milk are ingesting consuming 750 ml of milk per day with 3% fat
from 5.5 to 150.6 mg/kg of body weight per day would take in approximately 5 ppt per day.
(Waliszewski et al., 1996). (The Total Daily
Intake [TDI] guideline for DDT is 20 mg/kg of
Table III-1: Concentrations of DDE in Human Milk Fat in non-Aboriginal and Aboriginal
Populations [adapted from Jensen, J., K. Adare, and R. Shearer (eds.) Canadian Arctic
Contaminants Assessment Report. (Ottawa, Ontario, Canada: Department of Indian Affairs
and Northern Development, 1997)]
Location Year Mean concentration (ppt lipid)
Southern Canada 1992 222
Southern Quebec 1989/1990 340
Lower North Shore Quebec 1991 823
Nunavik, Northern Quebec (Inuit) 1989/1990 1212
Greenland (Inuit) 1993 3844
33
Table III-2: DDE Concentrations in Newborn Cord Blood Samples in Canada (sampled in
1993-1995) [adapted from Jensen, J., K. Adare, and R. Shearer (eds.) Canadian Arctic
Contaminants Assessment Report. (Ottawa, Ontario, Canada: Department of Indian Affairs
and Northern Development, 1997)]
Population p,p’-DDE Concentration p,p’-DDT Concentration
(ppm) (ppm)
Dene/Metis NWT* 0.32 0.02
Non-Aboriginals NWT 0.63 0.04
Southern Quebec 0.66 0.03
Nunavik, Northern Quebec (Inuit) 1.28 0.06
NWT (Inuit) 0.47 0.03
*Northwest Territories
that agonism by the estrogen mimicking isomer,
DDT and Reduction in Lactation
o,p‘-DDT may be the reason for the shortening
Endocrine disruption may have an indirect of duration, primarily because estrogen is
effect on the developing infant by reducing the known to reduce milk volume. Humans are not
amount of breast milk it can obtain. It is known the only species that breast feed their young –
that concentrations of DDE in the body of a all mammals do – and the biological
lactating mother can shorten the duration of mechanisms for bioaccumulation of DDT and
lactation (Gladen and Rogan, 1995; Rogan et passing it along to infants are the same.
al., 1987). This relationship was first noted in
women from the general population in North
Carolina. Women with concentrations of DDE
Levels of DDT and Effects in Other
in breast milk ranging from 0.31 to 2 ppm had a species
median duration of lactation of 26 weeks while
those with higher concentrations showed a Eggshell thinning
decrease in duration as DDE increased. Those DDE has been identified as the principal
with 5 to 23 ppm had median values ranging pollutant causing eggshell thinning and
from 9 to 10 weeks (Rogan et al., 1987). Gladen reproductive failure in predatory birds. Since the
and Rogan (1995) extended this study to banning of DDT in the early 1970s, many of the
Tlahualido, Mexico where further evidence bird populations facing extinction in the 1960s
suggests that DDE shortens the duration of and 1970s have recovered. However, there are
lactation. In this study, the duration of lactation instances where DDE levels in eggs and prey
ranged from 7.5 months for women with 0 to 2.5 species around the world are still high enough to
ppm to a median duration of 3.0 months for cause reproductive failure in recent times (Table
those with 12.5 ppm or greater. They proposed III-3).
Table III-3: Eggshell Thinning in Predatory Birds
Species/Location Concentrations Endpoints Critical Reference
in eggs concentrations
Bald DDE: 4-20 ppm 10% of population had Egg: 5 ppm DDE Anthony et
Eagles/Columbia thinner eggshell Egg: 15-20 ppm al., 1993
River Estuary (1980- Only 30% of the nests DDE reproductive
1987), USA had fledging young failure
Peregrine Falcons/ DDE: 4.5 (0.8-28) 15% thinner eggshell Eggshell critical Johnstone et
Rankin Inlet, NWT ppm w.w. 28% of the sample thickness: 17% of al., 1996
(1991-1994), had eggshell thinner average pre-DDT
Canada than critical level shell thickness
34
Species/Location Concentrations Endpoints Critical Reference
in eggs concentrations
Peregrine Falcons/ DDE: 7.6 (1.8- 16% thinner eggshells Court et al.,
Keewatin District/ 29.3) ppm w.w. eggshells with 29% 1990
Rankin Inlet (1981- thinner than pre-DDT
1986), Canada average did not hatch
Peregrine Falcons DDE: 2-5 ppm 11% thinner eggshell Henny et al.,
(1991), Russia w.w. 1994
African Goshawk ΣDDT: 18-326 18% and 22% thinner Critical level: 130 Hartley and
(1988-1991), ppm d.w. eggshell 35% to 45% ppm d.w. Douthwaite,
Zimbabwe population decline 1994
DDT continues to be found in certain wildlife in the Northwest Territories still suffer from
and human tissues throughout the world at eggshell thinning. And, based on residue levels,
concentrations able to cause population-level it is probable that reproduction in many other
effects. The bald eagle population in the populations of fish-eating birds and birds of
Columbia River Estuary and Peregrine falcons prey are also affected.
Table III-4: Action and Advisory Levels for DDT and Metabolites
Agency DDT and metabolites criteria
Great Lakes Water Quality Agreement Objectives (whole fish) 1 ppm wet weight
Health Canada, Tolerable Daily Intake (TDI) 20 ppb/day
FAO/WHO, Tolerable Daily Intake 20 ppb/day
WHO, Drinking water guideline 1 ppb
WHO DDT Guideline, milk (in fat) 1 ppm
US Food and Drug Administration Action Level for fish (wet weight) 5 ppm
Health Canada, maximum allowable concentration
Fish 5 ppm
Eggs and fresh vegetables 0.5 ppm
Dairy products, meat and meat by-products 1 ppm
Drinking water 1 ppm
Michigan Department of Public Health, fish consumption advisories 5 ppm
US EPA Minimal Risk Level (MRL) 0.5 ppt/day
US EPA recommended action level:
Most fruit and vegetables 0.1- 0.5 ppm
Eggs 0.5 ppm
Grain 0.5 ppm
Milk 0.05 ppm
Meat 5 ppm
Routes of Exposure
absorbed by inhalation, direct contact with skin
(dermal exposure), or oral ingestion
Overview of pathways
during pesticide preparation (mixing) or
For DDT, oral exposure through the ingestion of application (IEM on POPs, Annex II). Once
contaminated foods is considered to be the most sprayed, DDT does not disappear or degrade
important exposure route (ATSDR, 1993). into harmless byproducts. A stable and
However, these substances may also be persistent substance, it can easily move on soil
35
or dust particles and through waterways to end WWF commissioned the development of a
up in aquatic and terrestrial ecosystems both ―mass balance‖ model to explore this issue
near and far. DDT then moves up the food web further. It provides an accounting of the fate of
and because of its lipophilic nature, DDT and other pesticides used for indoor house
bioaccumulates at high concentrations in the fats spraying (Feltmate et al., 1998). The model uses
of fish, birds, and animals, including humans. A the concept of fugacity - the tendency of
certain level of DDT due to historical uses chemicals to move from one or more
continues to cycle through ecosystems. It is ―compartments‖ of the environment to others -
appropriate to inquire if vector-control uses such to estimate how the pesticide moves, over what
as indoor spraying add to these levels. period of time, and where the pesticide will end
up. The key parameters used in the model are:
Levels From House Spraying – A model
and assessment of the fate and exposure of the basic physical and chemical
DDT properties of the pesticide;
DDT is sprayed on the walls of homes and the physical characteristics of the room
other buildings as a control measure mainly and its contents;
against Anopheline mosquitoes for control of
malaria, and sand flies (Phlebotomus) for the affinities of the pesticide for different
control of leishmaniasis. The use of DDT for components of the environment, for
indoor house spraying has generally been instance with DDT, its affinity for fat
assumed to be a minor source of exposure to versus air or water;
residents. This may have been the situation
when DDT was in widespread and voluminous the rates of phase transfer, e.g.,
use in agriculture in the 1970s and before, and degradation and vapourization; and,
also a prevalent contaminant in the food web.
For instance, the 1993 review for WHO of anti- the behaviour of the people in the room,
malaria tools considered pre-1977 data showing e.g., inhalation and food consumption
comparable DDT residues in the fat of residents rates.
whose houses were regularly sprayed with DDT
and in the general population (Mouchet, 1994). The objective of the model is to provide a
However, recent data indicate that many of the quantitative picture of the fate of DDT or other
highest concentrations of DDT residues in pesticides which are sprayed indoors. Of
humans are in areas where indoor house particular interest are the extent of uptake by
spraying with DDT is a common vector control residents and extent of migration to the outdoor
measure although it cannot be ascertained environment.
whether there is unauthorized agricultural use as
well (Bouwman et al., 1991). Conversely, The mathematical model yields an estimate of
concentrations are declining where DDT use has the applied pesticide that remains on the walls;
been discontinued. is transferred to air, food, and other
―compartments‖ of the house via different
In addition, there persists an assumption that the routes; is transferred to the outside environment
use of DDT indoors contributes only tiny via different routes; is taken up by residents via
amounts of DDT to the environment (Mouchet, different routes; is degraded, etc. In this case,
1994). As DDT use has been deliberately and the model only addresses a single adult male
effectively scaled back in agriculture, the inhabitant. The very different behaviour,
potential for indoor house spaying to contribute consumption patterns, and inhalation rates of
more to residents‘ body burden of DDT, and to children, especially their frequent hand to mouth
environmental contamination, increases. activity which exposes them to a great deal more
contaminants via ingestion and dermal exposure,
36
were not modelled but could conceivably yield Remaining on wall surface.
quite different results. The potential transfer of
Between 120 to 270 grams (18 to 40%) remain
DDT to infants via breast milk has not been
on the wall and other surfaces 180 days (6
modelled either.
months) after the initial application. In the
The mass balance model estimated the fate of indoor environment, with limited light and
DDT 180 days following a single application of biological activity, degradation of DDT would
670 grams applied at the rate of 2 grams per be especially slow. Subsequent applications will
square meter. Because of uncertainties in certain cause some build-up, but within a year or so a
model parameters, for example the room steady state situation will develop in which
ventilation rate, the quantities are given as there is a fairly constant average amount of
ranges rather than as single values. between 400-500 grams remaining on the wall
surfaces, with the range being from 100-800
Physical removal and transfer of grams and the rate of application and the rate of
DDT to outdoors. loss from the room approximately equal. With a
room of 360 square meters, this corresponds to
Between 400 to 550 grams (60 to 82%) of the
1.1 to 1.4 gram per square meter. While still
total DDT applied is physically removed from
almost half of the DDT applied, it is a much
the walls and transferred outdoors. The model
lower amount than the 2 g/m2 strived for as an
assumed that, because of its crystalline form,
active dose. This would explain why standard
DDT would flake off the walls and onto
efficacy tests to measure mosquito mortality
surfaces, and would ultimately be mopped or
show reduced contact insecticidal performance
swept outdoors. Alternatively, the DDT could
with time.
be removed from the walls by washing and
transferred to the outdoor environment via
Human uptake.
washwater, as surveys conducted by WWF in
Mexico indicate. The one adult male resident is estimated to take
up DDT from the indoor application in the order
Absorption into food. of 1 microgram per hour or 20 micrograms per
day by inhalation. This represents a very small
DDT is likely to be absorbed from air and dust
fraction of the DDT applied. Although
into food, especially fatty foods such as butter
concentrations in the air are calculated to be
and milk which have a high affinity for DDT.
much higher than those in the outside air,
The concentrations achieved in the food may be
inhalation is a relatively unimportant route of
quite large - in the range of parts per million -
human exposure. On the other hand, uptake
but the total mass of DDT in the food will be
through consumption of food into which DDT
small compared to the mass in the room, i.e. less
has deposited or migrated and dermal contact
than 1 gram.
are significant routes of exposure. The latter
would be especially relevant for those who clean
Evaporation.
the walls and floors, and for infants and children
Direct evaporation from the wall is calculated to who are in regular contact with contaminated
be minimal but does occur constantly and is surfaces.
based on the chemical‘s vapour pressure.
The total uptake over a 6 month period is
However, since concentrations indoors are
estimated to be in the range of 0.1 to 0.3 grams.
calculated to be three orders of magnitude
Since approximately 50% would be excreted,
higher than in outdoor air, it is certain that there
there is a net retention of 0.05 to 0.15 grams
is transfer of DDT to the outdoors in the
total DDT in the fat. The model estimates that,
gaseous phase.
with continuous exposure, i.e., every 6 months,
concentrations of DDT in the fat would increase
over time in the range of 3-9 ppm of fat per year
for an adult male. However, this would not
37
continue indefinitely since, after approximately imported foods by the United States, Europe,
five years, the concentration would start to level and some Asian countries reflect health
off at 10 to 30 µg/g fat. This reflects a saturation authorities‘ concerns about human health
point in the body and is within the range impacts. Where malaria control programs spray
actually found in human fat in regions of the houses repeatedly, DDT residues in
world where DDT is used or highly householders and applicators are particularly
concentrated. high (Bouwman et al., 1991). Illegal agricultural
applications of DDT also serve to compound
There are few experimental or monitoring data
impacts on human health.
against which to validate the results of this mass
balance model, although actual data on residue While the human data on the health effects of
levels on walls and surfaces, of DDT low-dose exposures and endocrine disruption
concentrations in air, food, and residents‘ fat effects are sparse at this point, there is a large
should not be difficult to obtain. The model body of evidence regarding exposures, residues,
would also benefit from refinement of the input and health effects in wildlife. Given that many
data, including food storage and consumption essential biochemical processes are common to
patterns, cleaning behaviour, and specific all species, it would seem prudent to regard
information about children‘s food consumption effects on such processes in other species,
and indoor behaviours. including humans, as potentially significant.
Summary
Using the mass balance model as a screening
IV. RECOMMENDATIONS
tool indicates, overall, that much of the pesticide FOR RESEARCH
sprayed on walls and furniture during indoor
spraying operations ends up outdoors. In Formulating disease-vector-control strategies
addition, a small but significant amount is requires a complex assessment and balancing of
transferred via food to residents, which can a broad range of factors including effectiveness,
contribute substantially to their body burden of cost, sustainability, nature of the disease threat
DDT. (morbidity vs. mortality) and such
environmental considerations as impacts on
non-target species and hazards to workers
Synthetic Pyrethroids handling chemicals and humans living in treated
Synthetic pyrethroids are being substituted for environments. Despite some questions raised
spraying DDT in houses and they are the only about their cost, synthetic pyrethroids in
chemicals available for impregnating bednets. particular appear to be growing in popularity as
The limited research conducted to date on an alternative to DDT, especially since they are
synthetic pyrethroids is insufficient to fully not as persistent and bioaccumulative as DDT.
assess exposure to them.
The weight of scientific evidence regarding the
connection between wildlife health and human
Interpretation of Human Exposure health is growing. Adverse health impacts
Data observed in wildlife and laboratory animals
Many human populations depend on fish and from concentrations of DDT and other POPs are
other wildlife for a large portion of their diet. indicators of the potential human situation
Thus, they may accumulate high levels of because biological processes of the endocrine,
persistent pesticide residues, including DDT, immune, nervous, and reproductive systems are
from these sources. Inuit in northern Canada are common to all animals. WHO‘s scientific
one group whose traditional diet and mothers‘ experts appear to have focused largely on what
milk have become dangerously contaminated. might be called traditional health endpoints -
The strict pesticide residue regulations on cancer and acute toxicity. There has been little,
if any, attention to the new science on
38
transgenerational impacts of DDT and other doses in the womb or post-natally. The need for
pesticides. Since WHO‘s last significant review attention to low doses is signaled in a number of
of DDT in a public health context occurred in laboratory studies. For example, researchers
1993, and most of the scientific literature on the (Nagel et al., 1997) have found that a 2 ppb
impacts of these hormone-disrupting chemicals (parts per billion) dose of the plasticizer
on reproductive, neural, immune, and bisphenol A administered to pregnant mice led
behavioural outcomes post-dates this review, to a significant increase in their male offspring‘s
this is not surprising. There is now a prostate weights; this dose is 25,000 times lower
compelling, science-based case for the re- than the 50 ppm (parts per million) dose that
examination of DDT and other recommended was previously reported to be the No Observed
chemical alternatives. Adverse Effects Level (NOAEL) for bisphenol
A (vom Saal, 1997). Other researchers working
A survey of the currently published literature
with PCBs (polychlorinated biphenols) found
involving vector control pesticides highlights
significant neurotoxic effects in the offspring of
the need for much more research in order to
exposed female rats, effects that showed up at
better understand the range of impacts on both
low doses but were not evident at high doses
humans and wildlife. In particular, assessment
(Holene et al., 1995). Dutch researchers looking
of the hazards associated with the ‗newer‘
at PCBs, dioxins, and furans report that
chemicals which are replacing DDT are needed.
―relatively subtle adverse effects on
It is crucial for research to consider a broad
neurobehavioural development and thyroid
range of endpoints including subtle effects on
hormone alterations have been observed in
the immune system and nervous system,
infants and children exposed to background
reproductive outcomes, as well as behavioural
levels‖ (Brouwer et al., 1995).
impacts. While this paper cannot provide a
detailed listing of specific research objectives,
given the broad potential for endocrine Testing for Transgenerational
disruption related effects, it is clear that research Effects
should focus on low-dose testing, testing for
transgenerational effects, and the assessment of Recent statements from government officials
synthetic pyrethroid exposure to children and and concerned scientists have clearly indicated
the developing fetus from bednets. that current regulatory approaches to toxic
chemicals fail to address the special health
needs of infants and children. Scientists now
Low-Dose Testing acknowledge that it is not sufficient to assess
Traditional government-mandated toxicology effects only on infants and children, but it is
testing, as noted numerous times in this paper, necessary to go even further back in time – to
focuses on administering high doses of focus more systematically on the role of
chemicals, usually to adult animals. But a new chemical contaminants on the developing
paradigm of concern is emerging, specifically embryo and fetus. Reacting to reports of adverse
with regard to hazards associated with the health effects in wildlife and laboratory animals,
exposure of fetuses and embryos to extremely researchers are increasingly targeting in humans
low doses of chemicals that disrupt the the very critical 266 days from conception to
hormonal systems of the body. Organisms can birth, and exposure during that time to outside
be chronically exposed to such doses in the chemicals that bypass protective blood and
environment. placental barriers. The remarkable sensitivity of
the fetus and embryo to extremely low doses of
Traditional screening and testing programs for chemicals (both industrial chemicals and
assessing hazards from pesticides and other pesticides) means their exposure to
toxic chemicals are not designed to capture the extraordinarily low amounts of toxic chemicals
full range of undesirable effects of chemicals, can dramatically influence their future
particularly effects from exposures to very low development and well-being.
39
Assessment of Synthetic Pyrethroid The precautionary principle, as a general
Exposure to Children and the approach to environmental policy, is not entirely
new. It already forms the basis of at least a
Developing Fetus from Bednets dozen treaties and laws, including the 1987
As the house-spray modeling indicated, there Montreal Protocol on Substances That Deplete
are critical questions which should be answered the Ozone Layer, the 1990 Massachusetts
empirically regarding the resident and Toxics Use Reduction Act, the 1992 United
environmental exposure from indoor spraying Nations Framework Convention on Climate
and the use of bednets. While all alternatives to Change, and the 1994 Maastricht Treaty of the
DDT ought to be examined for their endocrine European Union. Sweden‘s interpretation of the
disruption potential at low doses, it is especially precautionary principle includes a substitution
important to test the synthetic pyrethroids clause enacted in 1991. This includes avoiding
because pregnant women and children around chemical products for which less hazardous
the world will be exposed to them inside their substitutes are available. The law also states that
homes and under bednets on a continuing basis. a scientifically-based suspicion of risk shall
These hazards may prove to be quite low. Even constitute sufficient grounds for the government
if they are sizable, these hazards may be worth to take measures against a chemical (Hileman,
incurring if the alternative is a high risk of death 1998).
or severe disease resulting from contact with
The precautionary principle places much
disease-bearing vectors. But these should be
fully-informed decisions, and where lacking, the
appropriate data should be developed
expeditiously.
In Closing – the Precautionary
Principle
The release and use of toxic substances, the
exploitation of resources, and physical
alterations of the environment have had
substantial unintended consequences affecting
human health and the environment. Growing
evidence of high rates of learning deficiencies,
asthma, cancer, birth defects, and species
extinction; along with global climate change,
stratospheric ozone depletion, and worldwide
contamination with toxic substances, has moved
some countries to adopt policies based on the
precautionary principle. According to the
precautionary principle, when substantial
scientific evidence suggests good reason to
believe that an activity, technology, or substance
may be harmful, action should be taken to
prevent harm. In other words, if an activity
raises threats of harm to the environment or
human health, precautionary measures should be
taken even if some cause and effect
relationships are not fully established
scientifically (Wingspread Statement on the
Precautionary Principle, 1998).
40
41
less emphasis on risk assessment and cost-
benefit analysis than does current practice.
Moreover when not enough is known about a
proposed product or activity and its alternatives
to do rigorous risk assessments and cost-benefit
analyses, the precautionary principle can
nevertheless be applied using a weight-of-
evidence approach. This takes into account the
cumulative evidence from many studies, often in
several species, that address whether a product
or activity will or is likely to cause injury.
42
43
less emphasis on risk assessment and cost-
benefit analysis than does current practice.
Moreover when not enough is known about a
proposed product or activity and its alternatives
to do rigorous risk assessments and cost-benefit
analyses, the precautionary principle can
nevertheless be applied using a weight-of-
evidence approach. This takes into account the
cumulative evidence from many studies, often in
several species, that address whether a product
or activity will or is likely to cause injury.
Since vector control methodologies like DDT
pose potential health effects that may be diverse
and long-term, rigorous application of the
precautionary principle as outlined above is
warranted.
44
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