Environmental Health Perspectives Volume
103, Supplement 4, May 1995
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Defining the Role of Pollutants in the Disruption of Reproduction in
Wildlife
Jo Ellen Hose1 and Louis J. Guillette2
1Department of Biology, Occidental College, Los Angeles, California;
2Department of Zoology, University of Florida, Gainesville, Florida
Abstract
Although chemical exposure has been associated with reduced reproduction
in certain North American fish, reptiles, and mammals, definitive cause-and-effect
data are lacking in many instances. Because the increasing use and global
transport of industrial chemicals pose significant risk to successful reproduction,
methods should be developed that can define the geographic extent and magnitude
of injury and risk to wildlife. Because industrial chemicals are articles
of commerce, information about injury to wildlife has been contentious and
too often ineffective in changing societal behavior. The following strategies
are advocated for inferring causal relationships. First, a balanced and
comprehensive assessment of the data is necessary to determine the geographic
extent of exposure and reproductive effects associated with environmental
pollution. Initial efforts to document reproductive injury should focus
on specific ecosystems in which detrimental effects have been observed,
but lack sufficient causal data. Model systems (including experimental mesocosms
or field ecosystems) should be identified or designed that can adequately
test multigenerational reproductive effects. Mechanistic data from supportive
laboratory studies on reproductive toxicity, quantitative structure-activity
relationships, and bioaccumulation can be used to predict effects of related
pollutants and to determine risk. Such information is essential to prevent
future injury to wildlife and to prioritize the numerous remediation decisions
facing our society. -- Environ Health Perspect 103(Suppl 4):00-00
(1995)
Key words: pollution, hormones, reproduction, wildlife, resource
management, environmental toxicology, wildlife toxicology
This paper was presented at the Conference on Environmentally
Induced Alterations in Development: A Focus on Wildlife held 10-12 December
1993 in Racine, Wisconsin.
We thank Dr. Theo Colborn, the C.S. Mott Foundation, the
National Fish and Wildlife Foundation, and the Johnson Foundation for bringing
together North American wildlife biologists to view their work on the effects
of contamination in wildlife in a global context.
Address correspondence to Dr. Jo Ellen Hose, 2590 Softchess
Pl., Arroyo Grande, CA 93420. Telephone (805) 544-4421. Fax (805) 545-8804.
Introduction
In the last 50 years, increasing production and use of industrial chemicals
has led to the worldwide contamination of ground water, lakes, and oceans
(1). Contaminants can enter the food chain and some can subsequently
bioaccumulate in wildlife. A few of these chemicals have been associated
with reproductive injury in wildlife (2-7). In December 1993, a group
of North American wildlife biologists convened to critically assess evidence
of specific instances where these contaminants were reported to produce
deleterious effects in wildlife populations through interference with reproduction
or embryonic development. Because of the large historical database on the
Laurentian Great Lakes, the majority of the studies focused on this area,
although reports were also presented on lakes in Florida, coastal Florida,
Arkansas, New York, the western coast of the United States, the Saint Lawrence
River, and British Columbia, Canada. These reports are presented elsewhere
in this volume.
The goals of this conference were 2-fold: to determine the geographic
scope and magnitude of reproductive and developmental effects in wildlife
on the North American continent, and to determine any commonality of the
causes or mechanisms accounting for the observed changes. The participants
in the conference concluded that:
- Throughout North America, there is widespread exposure to environmental
chemicals capable of disrupting development and the reproductive, nervous,
immune, and endocrine systems in
animals (8).
- Many of these contaminants mimic or inhibit hormones, thereby modifying
development and reproduction. There is convincing evidence for detrimental
effects of these contaminants in certain wildlife populations of North
America (1).
- However, we are uncertain of the geographic extent to which contaminants
contribute to the degradation of wildlife populations, and data from mechanistic
studies must be available before detrimental effects can be predicted.
This exercise convinced us of several points regarding our role as scientists
in our rapidly changing world. Most important, it is our responsibility
to provide the best available information to environmental managers even
in the face of incomplete answers. Over a thousand chemicals are introduced
annually into the environment (9), and complete toxicity information
on every chemical for the exposed wildlife will never exist. Thus, despite
testing and precautions, wildlife populations are at risk of injury.
One approach that might be useful when injury occurs is the ecoepidemiological
inference method outlined by Fox (9) that is based upon traditional
human epidemiology. The ecoepidemiological approach also has value for weighing
evidence to determine if the relative risk warrants policy changes. Another
strength of the ecoepidemiological method is its predictive power. For example,
knowledge of mechanisms of actions can allow the prediction of biological
effects of related compounds (10,11) and more accurate risk assessment
(12). Such inferential information is extremely powerful for predicting
and preventing detrimental effects on wildlife and frequently essential
for regulatory decisions.
Recommendations for Environmental Risk Assessment
It is now essential to develop methodologies to assess to what degree
endocrine-disrupting chemicals contribute to the continental and global
population decreases currently reported. For example, a number of studies
have clearly shown that wildlife exposed to various estrogenic contaminants
under laboratory conditions exhibit symptoms mimicking those of wildlife
living in close association with major contaminant sites (1). Theoretically,
endocrine-disrupting contaminants have the potential to cause catastrophic
declines in global wildlife populations. At specific localities, these compounds
have caused massive decreases in wildlife populations and have apparently
inhibited the recovery of many populations due to their multigenerational
effects (1). However, the global influence of these compounds must
be determined. Our working group (which also included Charles Peterson,
Malcolm Ramsay, and Donald White) proposed several specific areas of study
that would define the role of pollutants in causing reproductive injury
to wildlife and improve our predictive abilities for environmental risk
assessment.
Recommendation One
A balanced and comprehensive assessment of the data should be conducted
linking exposure and reproductive injury to wildlife on a continental and
global basis. Documentation and critical assessment of observational associations
between contaminants and wildlife declines are essential because toxicologists,
ecologists, and resource managers infrequently interact, and there appears
to be a general reluctance among resource managers to consider that toxic
chemicals can effectively reduce exposed populations (13-15). Most
field studies yield associations between reproductive injury and chemical
contaminants, not definitive cause-and-effect relationships. The evidence
for causality of reproductive injury can be systematically examined using
the ecoepidemiological criteria proposed by Fox (9). For an individual
data set, this approach provides a measure of the association's probability,
chronological relationship with exposure, strength of the association, and
specificity (9). Information from different data sets can be synthesized
to evaluate other criteria of causal inference (consistency on replication,
predictive performance, and biological coherence).
At present, a comprehensive synthesis of the various data sets linking
exposure and wildlife effects has been performed on only one geographic
region, the Laurentian Great Lakes. The Fox criteria (9) were applied
at the First Cause-Effect Linkages Workshop in 1989. A subsequent study,
"Great Lakes--Great Legacy," drew on those data and other work
to demonstrate the extent of the injury (16). The first Wingspread
Conference in 1991 clearly showed that sublethal, multigenerational effects
of endocrine-disrupting contaminants were responsible for a significant
decline in many of the vertebrate (fish, bird, mammal) populations in and
around the Laurentian Great Lakes (1). This type of synthesis is
essential to direct future scientific research and modify environmental
policy. If we are to determine the effects on other populations throughout
the North American continent, and in fact worldwide, we need a comprehensive
database.
One of the greatest strengths of this synthesis would be an evaluation
of consistency among individual data sets involving different geographic
areas, times, populations, investigators, and research designs and would
be the basis for decisions using the weight of evidence approach. This information
could be incorporated into the Geographic Information System (GIS) format
and provide mapping of historical, current, and emerging pollution sources
as well as effects data. A GIS format would facilitate modelling of transboundary
pollutant flow, and information could be linked to other global processes
such as ozone depletion and habitat destruction. Implicit in this approach
is the need for an institutionalized, long-term funding commitment.
Recommendation Two
Model ecosystems should be developed to define the detrimental effects
of endocrine-disrupting contaminants in the field and to establish causal
linkages between contaminant effects and individuals, populations, and communities.
As discussed above, the majority of the currently available data on the
detrimental effects of endocrine-disrupting contaminants on North American
wildlife comes from studies performed in or around the Great Lakes or other
temperate aquatic ecosystems such as the Chesapeake Bay and the western
coast of the United States. More recent studies have begun to focus on other
aquatic ecosystems, such as the warm, subtropical, shallow lakes of central
and South Florida (17, 18). The emphasis on aquatic ecosystems is
primarily due to the fact that many of the chemicals that affect reproduction
are lipid-soluble, bioaccumulate through the aquatic food chain, and frequently
exert effects in highly visible species at the top of the food chain (1,8,16).
Obviously, a continental or global risk assessment of the these contaminants
to wildlife should also include data from currently underrepresented ecosystems
(e.g., terrestrial ecosystems such as temperate and tropical wetlands, deserts,
and high elevation communities) and from organisms on all trophic levels.
Currently, freshwater fish and birds feeding in lakes are the most extensively
studied organisms (1). Although global population declines are under
way for many amphibian (19-21) and chondrichthian (22,23)
species, no published studies are available on the biological effects of
sublethal doses of chemicals with known endocrine-disrupting or reproductive
activities in these species. Could these declines be attributed, in part,
to the deleterious effects of such contaminants?
Until the recent meeting organized by the World Wildlife Fund, few opportunities
have existed for biologists from varying disciplines to discuss their concerns
and data on this topic with a continental or global perspective. A clear
consensus from the meeting called for future research to define model systems
that could be used to document multigenerational reproductive effects. These
model systems could be controlled mesocosms that are representative of an
ecosystem of interest or dedicated field study areas such as the Great Lakes
watershed (24-26). Properties of the ideal model must first be identified
by an interdisciplinary team interested in evaluating that particular system.
These properties will probably be unique to each system, target species,
or contaminant of concern. Initially the most useful model systems are expected
to be field study areas in which detrimental effects have been observed
at the organismal or population levels, but which lack sufficient cause-and-effect
support.
For example, many of the highly contaminated sites identified throughout
North America (e.g., U.S. Environmental Protection Agency's Federal Priority
Listing of SuperFund Sites) are frequented by both local and migratory wildlife
populations and have been studied by various university or governmental
agency-based scientists. The majority of these studies, however, have been
limited due to funding and technical expertise as they were conducted by
individuals or single agencies. Identification of some of these sites as
model ecosystems could rapidly stimulate interdisciplinary approaches that
would yield the data needed not only to document wildlife injury but also
to construct predictive models and ultimately stimulate policy changes.
Interestingly, this approach may yield the most rapid data gain, as ecological
studies usually require years of intensive research before patterns emerge.
Many of these ecological studies have already been performed, but a complete
interpretation of the results and assessment of risk is lacking due to paucity
of causal or mechanistic data. For example, laboratory-based causal data
were rapidly obtained once ecological studies identified that the population
collapse of several avian species was due to eggshell thinning (27).
Thus, a more rigorous demonstration of cause and effect could be initially
reserved for a selected number of contaminants or chemical classes thought
to have the most serious consequences based on ecological data. Likewise,
these causal studies would be linked with research on the physiological
(endocrine) mechanisms associated with embryonic development, reproduction,
immune system function, growth and metabolism.
Using the combined data sources established above, identified ecosystems
and species could rapidly be assessed. Through the use of model systems,
effects at the individual, population, and community levels could be linked
and relative risks calculated as the contaminant(s) flows throughout the
trophic system. Because environmental contaminants do not exist singly,
further studies should concentrate on evaluating contaminant synergism.
The interactive effects of contaminant mixtures can be evaluated using a
number of experimental designs. For example, full factorial design experiments
have been shown to be powerful in discriminating individual as well as interactive
effects (28,29). Studies of the interactive nature of complex contaminant
mixtures may also be done in a small number of field verifications of data
from laboratory bioassays, where much progress has been made to simplify
our understanding of contaminant interactions (30,31).
Recommendation Three
An improved scientific basis for risk analysis and prediction of reproductive
toxicity should be developed. This may be most effectively achieved by integrating
assays of common toxic mechanisms for reproductive injury, quantitative
structure-activity relationships (QSARs), and contaminant bioavailability/bioaccumulation.
Environmental risk analysis and prediction of deleterious effects on wildlife
should be based on an integrated set of data, including laboratory bioassays
and quantitative modeling for determination of dose effect where it is applicable.
Because many of the chemicals of concern affect development or mimic/inhibit
hormones (8), systematic testing of environmental contaminants must
include standard development assays as well as more innovative assays evaluating
hormonal disruption in target species. Multigenerational testing of contaminants
is also a priority, although few such assays are currently available for
wildlife.
Recent progress has been made in quantifying the effects of contaminants
and complex mixtures on wildlife using embryo development assays and in
vitro tests. Validated mortality/teratogenicity tests are available
which employ chicken (32), fish (33), and amphibian (34) embryos
as well as a number of freshwater and marine invertebrates (33,35).
Reproduction bioassays have also been developed for a number of freshwater
and marine plants (33,35). Data from the frog embryo test (FETAX)
(34) are now being used to predict the interactive effects of narcotic
chemicals, which provide the simplest model of additive mixture effects
(30,31). Assessment of complex mixtures with common toxic mechanisms
could be achieved using assays such as the rat hepatoma H4IIE bioassay system
(36-38), which is extremely promising for the evaluation of dioxinlike
toxicity and yields toxic equivalency factors (TCDD-equivalents) (11)
essential for modelling. Calibration of effects from egg injection studies
(39,40), laboratory exposures (41), and H4IIE bioassays will
facilitate risk assessment of environmental samples containing polyhalogenated
hydrocarbons. Similarly, an in vitro approach has yielded information
on the estrogenic equivalency of environmental chemicals (42) and
can be used with target wildlife species (43).
Ultimately, this information might be integrated into quantitative structure-activity
relationships (QSARs) capable of predicting toxicity/hormone activity of
untested compounds based on chemical structure, much the same way that carcinogenicity
and mutagenicity of polycyclic aromatic compounds can be predicted (10).
However, abiotic exposure measurements (such as soil or water) do not directly
translate into biotic effects because contaminant bioavailability and bioaccumulation
are often species- and site-specific (44). Obviously, exposure can
be more accurately estimated by measurement of tissue concentrations or
other measures of bioaccumulation in target organisms. For example, differential
trophic distribution of contaminants through the food chain is of great
importance for persistent, hydrophobic compounds where their association
with suspended sediment determines entry into biota (44). Although
at first appearance this may seem to complicate the prediction of toxicity
to the point of impossibility, application of these approaches to specific
model ecosystems might yield sufficient information to develop workable
predictive assessment tools.
There is currently enormous societal pressure to identify, curtail, and
clean up contaminated sites, be they chemical or nuclear contaminants. Given
the limited financial resources available, the great number of these sites
demands prioritizing them for remediation. As scientists, we must provide
guidance for these decisions that involve huge costs and dramatic societal
changes. On a global scale, we can intervene in many cases to prevent further
pollution of developing countries and undeveloped regions. Scientific decision
making should be shifted from being solely based upon data to an integration
of data, our professional experience, and practical inference. It is difficult
to advocate action in the face of scientific uncertainty, but too often
we minimize the power of the information we already possess. It is time
to broaden our role as scientists to develop a rationale for making urgent
environmental decisions through improved approaches to investigating injury
caused by contaminants, risk analysis, and predictive capability.
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