Introduction to Toxicology
EV 460/660 & BI 460/660
Fall 2014
Environmental Toxicology
1.
Environmental Toxicology – study of source, fate, and effects of chemicals in the environment
-- emphasis is on toxicants – poisons of anthropogenic origin
-- historically – little concern or regulation of chemical disposal, chemical release into air or water or
adverse effects of environmental chemicals
-- Love Canal, Silent Spring, founding of USEPA, and passage of Clean Air Act, Clean Water Act,
RCRA, CERCLA, and TSCA forced development of field of environmental toxicology
-- today – estimated that 100,000 different chemicals are released into the global environment
annually
2.
Environmental toxicology – two major areas of concern
-- impacts of environmental toxicants on human health
-- impacts of environmental toxicants on ecosystems and biotic constituents of ecosystems
3.
Historically, chemicals of major environmental concern have shown
-- environmental persistence
– long half lives in environment
-- resistant to abiotic and biotic degradation
-- bioaccumulation – tendency to concentrate in organism above ambient levels
-- biomagnification – tendency to increase in concentration across trophic levels
4.
Abiotic degradation processes
A.
Photolysis – light (primarily UV) breakage of chemical bonds
-- most likely to occur in atmosphere and surface waters where light intensity greatest
-- depends on both light intensity and capacity of toxicant molecule to absorb light
-- light energy may also facilitate degradation by hydrolytic or oxidative processes
B.
Hydrolysis – water, often in combination with light or heat, breakage of chemical bonds
-- rates of hydrolysis increase with increasing temperature and extremes of pH
5.
Biotic degradation
--microbial (bacteria and fungi) metabolism is primarily responsible
-- degradation rates typically much faster than abiotic processes alone
-- reactions include hydrolysis, oxidation, dehalogenation, ring cleavage, and dealkylation
6.
Non-degradative elimination processes
-- physical processes that relocate chemical from one region to a different area
-- atmospheric movements may disperse volatile chemicals, particulate matter, or chemicals sorbed
onto dust particles
-- water movements may move chemicals from land into water via surface runoff, disperse chemicals
in surface waters, or carry chemicals from the surface into soils and sub-surface water
through percolation and infiltration,
-- sorption of chemicals onto sediments may remove chemicals from the water column and deposit
them into bottom sediments
7.
Bioaccumulation and biomagnification
-- potential for bioaccumulation and biomagnification often positively correlated with lipophilicity
(lipid solubility) of chemical
-- aquatic and marine environments are major sites for bioaccumulation and biomagnification of
lipophilic compounds
-- aquatic and marine environments are often sinks for persistent chemicals
-- aquatic and marine organisms pass tremendous quantities of water through respiratory
and/or digestive structures allowing for efficient extraction of low levels of lipophilic
compounds from water
-- body burden concentrations may bioaccumulate to several orders of magnitude greater than the
concentration of chemical in the ambient environment, biomagnification can further increase
concentration of the chemical with each progressive link in the food chain (trophic transfer)
-- body burden concentrations of lipophilic contaminants often positively correlated with total body
lipid content
-- bioaccumulation of lipophilic toxicants can lead to delayed onset toxicity
-- compounds initially sequestered in lipid deposits are mobilized when lipid stores are
utilized
-- physiological stresses (inadequate food intake, migration, etc) and reproduction can
increase utilization of lipid stores
-- toxicants mobilized by utilization of lipid stores may undergo maternal transfer to offspring
via yolk development of eggs and lactation
8.
Similarities between toxicokinetics in individual organism and toxicokinetics in the environment
A.
Organismal absorption vs. environmental source
-- organismal entry via absorption through multiple routes – dermal, oral, inhalation, etc.
-- environmental entry via release from multiple sources of release – smoke stack, waste site,
discharge pipe, pesticide application, spill, improper disposal, etc.
B.
Organismal transport and distribution vs. environmental transport and distribution
-- organismal transport via blood and lymph, distribution to tissues based on blood flow,
chemical properties, tissue affinity, etc.
-- environmental transport via atmospheric and hydrologic processes, distribution based on
atmospheric and hydrodynamic flow, chemical properties, and affinity for environmental
constituents (i.e., soil organic matter, clay)
C.
Organismal transformation reactions vs. environmental transformation reactions
--organismal transformation reactions may result in detoxification/excretion or activation
-- environmental transformations may result in detoxification/degradation or activation
9.
Differences between toxicokinetics in individual organism and toxicokinetics in the environment
-- environmental systems are inherently more complex and variable than physiological systems of
individual organisms
-- many more routes of entry (sources of release) into the environment than routes of entry (absorption)
into organism
-- considerably more variability and complexity in environmental transport and distribution than in
organismal transport and distribution
-- more environmental compartments for distribution than organismal tissue/organ compartments
for distribution
-- species differences complicate organismal toxicology, but both species differences and abiotic
variables further complicate environmental toxicology
-- ability to experimentally control many variables during systematic in vivo and in vitro studies
facilitates understanding of organismal toxicology, lack of experimental control or difficulty
in experimental control of many variables hampers understanding of environmental
toxicology
10.
Sources of toxicants released to the environment
A.
Mass emission rate (g/h) = rate at which a toxicant is emitted by a source into the
environment
-- mass emission rate (g/h)
= toxicant concentration in the medium (g/m3) X flow rate of medium (m3/h)
B.
Point sources – discrete, identifiable, specific geographic location of chemical discharge, a
I.
II.
III.
IV.
V.
C.
11.
particular stationary place of entry of chemicals into the environment
some examples – a specific smoke stack, a particular pipe discharging effluent into a
receiving stream, a factory, a sewage treatment plant, a chemical waste dump, a
landfill, an oil or chemical spill
often relatively easy to determine mass emission rates, particularly for point sources
that are routinely monitored for compliance with environmental regulations
however, analytical measurement may be difficult due to: trace toxicant
concentrations in complex effluent chemical mixtures, difficulties in determination of
all relevant reactive metabolites or chemical forms, and temporal fluctuations in
toxicant concentrations and flow rates, also many non-regulated/monitored toxicants
of potential concern
often relatively easy to monitor, regulate, and control point source emissions of
toxicants into the environment
earliest and most well developed regulatory policy/law and pollution control
technologies aimed at point sources
Non-point sources – not a discrete, easily identifiable place of entry of chemicals into
environment
I.
some examples
-- diffuse emissions over widespread geographic areas – farm fields in rural areas,
lawns and streets in urban areas
-- multiple mobile sources of emissions – vehicles
-- multiple, dispersed stationary sources – septic tanks
-- atmospheric deposition from point sources and vehicle emissions
II.
very difficult to accurately determine mass emission rates
III.
very difficult to monitor, regulate, and control non-point source emissions of toxicants
IV.
current area of concern regarding needed development of regulatory policy/law and
pollution control technologies
Transport of toxicants in the environment – physical (non-biological) movement of released
chemical
-- following release into the environment, transport processes will determine spatial and
temporal distribution of the toxicant in the environment
-- transport medium is usually air or water
-- toxicant form in transit may be gaseous, dissolved, or particulate
-- two major forms of physical transport – advection and diffusion
A.
Advection – movement of the transport medium, chemical toxicant simply “goes along for the
ride” with the bulk movement of the medium
-- two types, homogeneous advection and heterogeneous advection
I.
Homogeneous advection -- movement in a single transport medium
-- examples – transport of chemical in air on a windy day or transport of a chemical
dissolved in water in a flowing stream
-- advective currents often dominate chemical transport in the atmosphere and
aquatic and marine systems
-- advective air and water currents also occur in soil systems, but the rate of
movement is considerably slower than in the atmosphere or bodies of water
II.
Heterogeneous advection – two (or more) transport media are involved in chemical
movement
-- examples –
--chemical transported in air undergoes atmospheric chemical deposition
into water or soil and is further transported in the second medium or chemical
--transport in water undergoes sorption to suspended particles and settles to
bottom to be further transported by sediment movement
-- dynamics of heterogeneous transport are more complex than dynamics of
homogeneous transport
B.
12.
13.
Diffusion – movement of the chemical toxicant itself, movement is from a region of relatively
high concentration to a place of lower concentration
-- may occur within a medium (or phase) or between media (or phases)
I.
Diffusion within a phase or medium
-- may occur by random (thermal) motion of the chemical (molecular diffusion), by
random turbulent mixing of the transport medium (turbulent diffusion), or by a
combination of both
II.
Diffusion between phases or media
-- occurs at interface between two media, air-water, particle-water, or biological
membrane-water
-- diffusive transport will drive a chemical between media until the equilibrium
concentrations are reached in each phase
Equilibrium partitioning – chemical added to two immiscible phases will partition between the two
phases according to its solubility in each phase, the concentration ratio at equilibrium is the
partition coefficient
A.
Air-water partitioning estimated by the ratio between a chemical’s vapor pressure and
aqueous solubility
-- chemicals that tend to pass from water into air have high vapor pressures and low aqueous
solubility
-- chemicals that tend to pass from air into water have low vapor pressures and high aqueous
solubility
B.
Lipid-water partitioning – most relevant to biological systems because of lipid content
of cell membranes and lipid stores of organisms
-- hydrophobic compounds tend to pass from water into lipids
-- often estimated by octanol-water partitioning, however, water solubility varies over a wider
range than octanol solubility
C.
Particle-water partitioning – many chemicals preferentially associate with soil and sediment
particles rather than the aqueous phase
-- can be estimated by the ratio between the concentration of chemical in the soil or sediment
and the concentration of chemical in water
-- complex interactions between chemicals and the organic carbon fraction of particles and
the mineral/clay phase of particles, thus partitioning is dependent upon the organic
carbon and mineral/clay composition of soil and sediment particles
Transformation processes
A.
Reversible reactions – continuous exchange among chemical states, usually abiotic
-- include: ionization, precipitation and dissolution, complexation, and chemical speciation
B.
Irreversible reactions – relatively permanent change of a parent chemical into a reaction
product (metabolite), both abiotic and biotic
-- include: hydrolysis, photolysis, oxidation-reduction (though many redox reactions are
reversible, included here because often are irreversible on temporal scales important
to environmental fate and toxicity), and biotransformation (primarily bacterial)