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Section B
The Toxicological Process
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The Toxicological Paradigm
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The Toxicological Paradigm
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Toxicokinetics
! Toxicokinetics is the quantitation of the time course of toxicants in
the body during the processes of absorption, distribution,
biotransformation, and excretion or clearance of toxicants
! In other words, toxicokinetics is a reflection of how the body
handles toxicants as indicated by the plasma concentration of that
xenobiotic at various time points
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Toxicokinetics
! Absorption: taking in a chemical from a site(s) of exposure,
resulting in an internal dose
! Distribution: distributing a chemical from its site of absorption
throughout the body
! Excretion: removing the chemical from the body
! Biotransformation: enzymatic modification of chemicals
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Toxicokinetics
! The end result of these toxicokinetic processes is a biologically
effective dose of the toxicant
! The biologically effective dose is that portion of the internal dose
that interacts with biological molecules
! Some interactions result in a biological effect—while others may not
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Toxicodynamics
! Toxicodynamics refers to the molecular, biochemical, and
physiological effects of toxicants or their metabolites in biological
systems
! These effects are result of the interaction of the biologically
effective dose of the ultimate (active) form of the toxicant with a
molecular target
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Molecular Targets Concept
! The toxic action of a chemical is a consequence of the physical/
chemical interaction of the active form of that chemical with a
molecular target within the living organism
! Some active forms are the chemical exposed to
- Other active forms are biotransformation products of the
chemical
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Examples of Molecular Targets
! Proteins
- Arylhydrocarbon (Ah) receptor
! Dioxin
Benzo[a]pyrene
! Hemoglobin—CO
! Acetylcholinesterase—organophosphate pesticides
! ! Lipids—carbon tetrachloride
! DNA—aflatoxin; benzo[a]pyrene diol epoxide
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How Does the Active Form Interact with a Target?
! Reversible: the active form can disassociate from the molecular
target
! Irreversible: the active form stays attached or bound to the target
- Usually involves a covalent bond between the chemical and
target molecule forming an adduct
- In some cases, the target can be repaired (fixed)
- However, the active form of the chemical still remains bound to
a molecule of the target
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Dose-Response Concept
! The magnitude of the toxic effect will be a function of the
concentration of altered molecular targets
! This is related to the concentration of the active form of the
toxicant( biologically effective dose) at the site where the
molecular targets are located
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The Toxicological Process
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The Toxicological Process
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The Toxicological Process
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Understanding Human Risk from Chemicals
Important for
understanding
toxicokinetic
processes
Characterizing
what altered
cellular
pathway(s) is
important for
toxicity
(toxicodynamics)
Critical
components for
risk assessment
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Understanding Human Risk from Chemicals
Important for
understanding
toxicokinetic
processes
Characterizing
what altered
cellular
pathway(s) is
important for
toxicity
(toxicodynamics)
Critical
components for
risk assessment
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Lecture Evaluation
Please take a moment to evaluate
this lecture. Your feedback is very
important and will be used for future
revisions. The Evaluation link is
available on the lecture page.
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