Current and Emerging Paradigms in Environmental Toxicology Lecture 2

Understanding the three basic functions in environmental toxicology 1. Interaction of toxicant (xenobiotic) with the environment Determines amount (dose) of toxicant available to living organisms Determines amount (dose) of toxicant available to living organisms Time component Time component 2. Interaction of toxicant with site of action Usually receptor on/in a cell Usually receptor on/in a cell Receptor often a cell protein Receptor often a cell protein 3. Interaction of toxicant at the molecular level, leading to all higher level ecological effects Line from molecular to ecological effects is poorly understood 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 Chemical/physical-chemical characteristics Chemical/physical-chemical characteristics Bioaccumulation/biotransformation/biodegradation Bioaccumulation/biotransformation/biodegradation Site of action Site of action Biochemical monitoring Biochemical monitoring Physiological and behavioral effects Physiological and behavioral effects Population parameters Population parameters Community parameters Community parameters Ecosystem effects Ecosystem effects

Chemical/Physical-Chemical Characteristics Interactions of xenobiotic compound with biological compounds determines toxicity Interactions of xenobiotic compound with biological compounds determines toxicity The degree of effect that is due to the physico-chemical characteristics of the compound is called the Structure-Activity Relationship (QSAR). The degree of effect that is due to the physico-chemical characteristics of the compound is called the Structure-Activity Relationship (QSAR). Has potential for allowing prediction of toxic effects based only on structure of xenobiotic. 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 Could save lots of time, money, effort while allowing a greater degree of protection

Bioaccumulation/Biotransformation /Biodegradation Many things can happen to chemical between release to environment and arrival at the biological site of action Many things can happen to chemical between release to environment and arrival at the biological site of action 1. Bioaccumulation – increase in concentration of chemical in tissue relative to concentration in environment More likely in lipid solubule/lipophilics More likely in lipid solubule/lipophilics 2. Biotransformation – chemical change in toxicant caused by biological tissue May decrease [usually] or increase toxicity May decrease [usually] or increase toxicity 3. Biodegradation – breakdown of a xenobiotic into a simpler chemical form Could be the result of biotransformation Could be the result of biotransformation All above processes dependent on site specific conditions so direction and degree hard to predict All above processes dependent on site specific conditions so direction and degree hard to predict

Receptor (site) and Mode of Action Active site extremely important on determining mode of action Active site extremely important on determining mode of action May cause very specific or very general effect May cause very specific or very general effect Active site may be on specific nucleic acids, enzymes, cell membranes or non-specific Active site may be on specific nucleic acids, enzymes, cell membranes or non-specific Covered much more in Xenobiotic Metabolism part of course Covered much more in Xenobiotic Metabolism part of course

Biochemical/Molecular Effects Broad range of possible effects Broad range of possible effects Could be general (ex. general effect on DNA) or specific (ex. effect of specific portion of DNA) Could be general (ex. general effect on DNA) or specific (ex. effect of specific portion of DNA) Includes effects on chromosomes, enzyme systems, immunological system, etc. Includes effects on chromosomes, enzyme systems, immunological system, etc.

Physiological and Behavioral Biochemical/molecular effects manifested at higher organismal level Biochemical/molecular effects manifested at higher organismal level Classical means by which population health is assessed Classical means by which population health is assessed Major drawback  extrapolation from individual effect to population and ultimately ecosystem effect 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 Can include pathology, oncogenesis, reproduction, mortality, osmo- and ionoregulation, behaviors (fish respiration, cough response), temperature preference, predator avoidance or prey detection

Population effects Suitable for both field and laboratory evaluations Suitable for both field and laboratory evaluations Well-developed protocols Well-developed protocols Population size, density, age-structure, cycling, growth rate, genetics Population size, density, age-structure, cycling, growth rate, genetics

Community effects Evaluation of community structure extensively used in field studies Evaluation of community structure extensively used in field studies Many indices developed to quantify species composition Many indices developed to quantify species composition Most widely used  species diversity (biodiversity) Most widely used  species diversity (biodiversity) Most dramatic impact that can be observed Most dramatic impact that can be observed Decrease in species diversity usually = impact but sometimes reverse is true 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 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 Most ecosystem-level changes indicate a serious problem 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 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 Evaluation of effects must be system-specific

Ecosystem effects Most environmental regulations aimed at protecting ecosystem structure and function but these are rarely measured when determining compliance Most environmental regulations aimed at protecting ecosystem structure and function but these are rarely measured when determining compliance

Complexity theory Alternative to previous “classical) approach to environmental toxicology Alternative to previous “classical) approach to environmental toxicology Based on differences between organisms and ecosystems Based on differences between organisms and ecosystems Organisms – genetic structure is retained in all cells (redundant) and designed to maintain homeostasis --> most impacts not passed on to future generations 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 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 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 Exhibit both deterministic and stochastic properties Exhibit both deterministic and stochastic properties Causes and effects of events experienced by systems are not proportional Causes and effects of events experienced by systems are not proportional Different parts are linked and affect one another synergistically Different parts are linked and affect one another synergistically Can undergo irreversible processes (because no system “memory”) Can undergo irreversible processes (because no system “memory”) Dynamic (not in equilibrium) Dynamic (not in equilibrium) Note: above properties may be useful in extrapolating toxicity test results on to highly variable ecosystems Note: above properties may be useful in extrapolating toxicity test results on to highly variable ecosystems

Spatial and Temporal Scales All previous functions vary over spatial and temporal scales All previous functions vary over spatial and temporal scales May appear disconnected but never are 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) 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) Type of environmental problem will be a function of spatial and temporal scale (see Figure 2.5)

Wednesday – Intro to toxicity testing