1. 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

2. Toxicology is an applied science with many areas of specialization
Images from Gray’s Anatomy
Images from webelements.com
Image from Molecular Cell Biology
What is so great about toxicology is that you are specialized but diverse all at the same time!!
Introduce the concept of dose w/ tetrodotoxin (fugu)

3. Who are Toxicologists?
Toxicology involves integration of information from
many different areas of expertise. People working in
toxicology can also be called:
Biochemists
Chemists
Pathologists
Cancer Researchers
Veterinarians
Medical Doctors
Cell and Molecular Biologists
Engineers
Mathematicians
Statisticians
Lab Technicians
Animal Care Providers

4. 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)

5. 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

6. 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?

7. 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

8. Descriptive Toxicology Toxicity Testing
Assesses the concentration-dependent hazard a chemical may present
Human health
Natural populations
Results typically applied to
Approval of product use
Regulating allowable concentrations in the environment.

9. 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

10. 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.

11. 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

12. 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

13. 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

14. 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.