Transcript Toxicology as a Discipline

What Do Toxicologists Do?
Most Toxicologists work to assess and understand
how chemicals affect living systems
• Develop mechanistic understanding of
effects
• Ensure safer chemical products
• Develop safer drugs & medicines
• Determine risks from chemical exposures
• Develop treatments for chemical
exposures
• Ensure a safe food and water supply
• Forensics
© 2008 Society of Toxicology
Toxicology is an applied science
with many areas of specialization
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Images from Gray’s Anatomy
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© 2008 Society of Toxicology
Who are Toxicologists?
Toxicology involves integration of information from
many different areas of expertise. People working in
toxicology can also be called:
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Biochemists
Chemists
Pathologists
Cancer Researchers
Veterinarians
Medical Doctors
Cell and Molecular Biologists
Engineers
Mathematicians
Statisticians
Lab Technicians
Animal Care Providers
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What are major areas of
specialization in toxicology?
• Mechanistic toxicology (basic biology
and chemistry)
• Descriptive toxicology (testing)
• Regulatory toxicology (rule making
and compliance)
• Risk assessment (modeling)
• Translational and clinical (applying basic
research to patient care)
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Mechanistic Toxicology
Focuses on how
• Chemicals produce adverse effects
• Biological systems protect
themselves against adverse effects
Involves
• Cellular and Molecular Biology
• Chemistry, often xenobiotic
metabolism
Xenobiotic: a chemical that is foreign to the
organism
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Mechanistic Toxicology
Chemical research in toxicology usually
investigates metabolic transformations of drugs
or potentially hazardous chemicals
• How persistent is a chemical in the
body?
• Are metabolic products toxic?
• Do test animals exhibit the same
results as humans or other
species of concern?
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Descriptive Toxicology
• Typically involves toxicity testing
• Broad spectrum of responses reflects toxicity
– Functional effects, such as immunological responses
– Growth inhibition
– Reproductive impairment
– Increase in cancer incidence
– Mortality
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Descriptive Toxicology
Toxicity Testing
• Assesses the concentrationdependent hazard a chemical
may present
– Human health
– Natural populations
• Results typically applied to
– Approval of product use
– Regulating allowable concentrations
in the environment.
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Descriptive Toxicology
Types of toxicity testing
• In vitro (test tube)—useful in detecting potential biochemical and
genetic effects
– Use model systems (bacteria, cultured animal cells, DNA interactions)
• In vivo (animal)—are essential for detecting health effects
– Acute, chronic, multi-generation
– Experimental animals may be treated with high doses over a lifetime
to evaluate potential to cause cancer
• In silico (computer-based)—biological
experiments conducted by computer
models; these depend on data previously
collected in other experiments
Completion of all toxicity tests may take
five or six years and is very costly
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Descriptive Toxicology
Toxicity Testing
• Molecular and cellular studies in
toxicology often supplement toxicity
testing results to help ascertain
chemical hazard. They often unravel
complex processes that underlie an
adverse response.
• Use of toxicants can help determine
the function of proteins in complex
networks.
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Descriptive Toxicology
What private and public sectors invest in toxicity
testing that aims to protect human health?
• Chemical Manufacturers
• Pharmaceutical Industry
• US Federal Agencies and Programs
– National Toxicology Program (NTP)
– Environmental Protection Agency
(EPA)
– National Institute of Environmental
Health Sciences (NIEHS)
– Food and Drug Administration (FDA)
• State and Local Governmental Bodies
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Regulatory Toxicology
• Setting rules and assuring compliance
– Product registration
– Allowable concentrations in food or environmental media
• Technical and legal issues may require negotiation and
gathering of new information
– Risk and safety are estimated by total weight of evidence
– Toxicity evidence is the basis, but often rules are modified by
political, legal considerations, as well a technical feasibility
© 2008 Society of Toxicology
Regulatory Toxicology
Risk Assessment
Is the mathematical modeling process
that yields estimates for safe or
allowable chemical concentrations
• Hazard identification
• Dose-response assessment
• Exposure characterization
• Identify unique effects of chemical
mixtures
• Risk assessment
• Risk characterization
• Right to know and understand
• Uncertainty characterization
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Translational
• Translational science is the application of biomedical research and
drug development to efficiently use a promising drug in the right
patient circumstances and assess its efficacy in the human using
appropriate indicators such as biomarkers.
• Scientists work in multidisciplinary teams
involving basic researchers, clinicians,
patient care providers, regulators, and ethics
boards.
• Basic scientists provide new tools for use in
patients and for assessment of their impact,
and clinical researchers make novel
observations about the nature and
progression of disease that can lead to
further basic research.
© 2008 Society of Toxicology