Transcript Current Paradigms in Environmental Toxicology

Current and Emerging
Paradigms
in
Environmental Toxicology
Lecture 2
Understanding the three basic functions
in environmental toxicology
Interaction of toxicant (xenobiotic) with the environment
1.
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Determines amount (dose) of toxicant available to living organisms
Time component
Interaction of toxicant with site of action
2.
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Usually receptor on/in a cell
Receptor often a cell protein
Interaction of toxicant at the molecular level, leading to all
higher level ecological effects
3.
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Line from molecular to ecological effects is poorly understood
Note: see Figure 2.1
Note: f(letter) = function of process indicated by letter
Classification of toxicological effects
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Chemical/physical-chemical characteristics
Bioaccumulation/biotransformation/biodegradation
Site of action
Biochemical monitoring
Physiological and behavioral effects
Population parameters
Community parameters
Ecosystem effects
Chemical/Physical-Chemical
Characteristics
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Interactions of xenobiotic compound with
biological compounds determines toxicity
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The degree of effect that is due to the
physico-chemical characteristics of the
compound is called the Structure-Activity
Relationship (QSAR).
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Has potential for allowing prediction of
toxic effects based only on structure of
xenobiotic.
Could save lots of time, money, effort
while allowing a greater degree of
protection
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Bioaccumulation/Biotransformation
/Biodegradation
Many things can happen to chemical between
release to environment and arrival at the biological
site of action
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1.
Bioaccumulation – increase in concentration of chemical
in tissue relative to concentration in environment
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2.
Biotransformation – chemical change in toxicant caused
by biological tissue
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3.
May decrease [usually] or increase toxicity
Biodegradation – breakdown of a xenobiotic into a
simpler chemical form
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More likely in lipid solubule/lipophilics
Could be the result of biotransformation
All above processes dependent on site specific
conditions so direction and degree hard to predict
Receptor (site) and Mode of Action
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Active site extremely important on
determining mode of action
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May cause very specific or very general effect
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Active site may be on specific nucleic acids,
enzymes, cell membranes or non-specific
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Covered much more in Xenobiotic Metabolism
part of course
Biochemical/Molecular Effects
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Broad range of possible effects
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Could be general (ex. general effect on DNA)
or specific (ex. effect of specific portion of
DNA)
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Includes effects on chromosomes, enzyme
systems, immunological system, etc.
Physiological and Behavioral
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Biochemical/molecular effects manifested at higher
organismal level
Classical means by which population health is
assessed
Major drawback  extrapolation from individual
effect to population and ultimately ecosystem effect
Can include pathology, oncogenesis, reproduction,
mortality, osmo- and ionoregulation, behaviors (fish
respiration, cough response), temperature preference,
predator avoidance or prey detection
Population effects
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Suitable for both field and laboratory
evaluations
Well-developed protocols
Population size, density, age-structure, cycling,
growth rate, genetics
Community effects
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Evaluation of community structure extensively used in field
studies
Many indices developed to quantify species composition
Most widely used  species diversity (biodiversity)
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Most dramatic impact that can be observed
Decrease in species diversity usually = impact but sometimes reverse is
true
Diversity can be misleading  can have same diversity after exposure
but be the result of a completely different set of species
Note: most of what we call communities are really assemblages
because we do not understand most of the interactions among
populations in a “community”
Ecosystem effects
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Most ecosystem-level changes indicate a
serious problem
Variables measured can include metabolism
(energy capture, flow, loss), net productivity
(gross productivity – respiration), biomass
accumulation, rate of detrital breakdown,
landscape alteration, species distribution,
chemistry
Evaluation of effects must be system-specific
Ecosystem effects
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Most environmental regulations aimed at
protecting ecosystem structure and function
but these are rarely measured when
determining compliance
Complexity theory
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Alternative to previous “classical) approach to
environmental toxicology
Based on differences between organisms and
ecosystems
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Organisms – genetic structure is retained in all cells
(redundant) and designed to maintain homeostasis --> most
impacts not passed on to future generations
Ecosystems – no central repository of information like
genome
History of past events written into ecosystem structure and
function, nature of interactions  high complexity and
non-linear relationships
Properties of Complex, Non-linear
Structures
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Exhibit both deterministic and stochastic properties
Causes and effects of events experienced by systems
are not proportional
Different parts are linked and affect one another
synergistically
Can undergo irreversible processes (because no
system “memory”)
Dynamic (not in equilibrium)
Note: above properties may be useful in extrapolating
toxicity test results on to highly variable ecosystems
Spatial and Temporal Scales
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All previous functions vary over spatial and temporal
scales
May appear disconnected but never are
Usually smaller spatial scale operates at a shorter
temporal scale because of inherent differences when
considering atom-level effects to ecosystem level
effects (see Figure 2.4)
Type of environmental problem will be a function of
spatial and temporal scale (see Figure 2.5)
Wednesday – Intro to toxicity testing