Mid Term One Flashcards
Discuss need for systems biological approaches in risk assessment of environmental health and toxicology
Need to recognize that the human body and the environment are biologically complexed and therefore interact with chemicals and xenobiotics in multiple complex ways that sometimes can not be seen in an controlled study, or when looking for one or a few markers, therefore you need to take the complexity into account when doing risk assessment to be conservative in your approach.
Understand current testing tools and their application to risk assessment
Tools include; high throughput screening, stem cells biology, functional genomics, bioinformatics, systems biology, computational systems biology, physiological based pharmacokinetic models, structure activity relationships, biomarkers, molecular and genetic epidemiology
Describe areas of application for systems biological approaches in environmental health
- Hazard and risk prioritization of chemicals Identifying mechanistic information to tailor chemical testing programs,
-Safety screening of food additives and foot contact products, Support approaches for aggregate and cumulative risk assessment, – –Estimating variability in response in a population, Pharmaceutical lead selection in drug development, Safety screening of pharmaceutical contaminants and drug
metabolites
Key points toxicology
Exposure: any condition which provides an opportunity for an external environmental agent to enter the body, depends on intensity and frequency of exposure.
Dose: the amount of agent actually deposited within the body, significantly different doses can result from the same exposure
Response: Biological effect of the agent
3 basic concepts in toxicology
•Dose/Response
•Exposure x Hazard = Risk
•Individual Sensitivity (age, size, gender, ethnicity, species, genetics,
environment)
Dose‐Response
effects of amount on the response of the induvial, lots of factors effect dose response, someone sensitive might have a higher response with the same dose. Think different people drinking alcohol. The dose effect can be linear (genotoxic chemicals) or non linear which assumes safe references doses or NOEL and LOEL amounts.
NOEL (NOAEL)
No Observable (Adverse) Effect Level; Highest point at which there was no (adverse) effect
LOEL (LOAEL)
Lowest Observable (Adverse) Effect Level; Lowest point at which there was an (adverse) effect
BMD10
Benchmark dose 10, where at that concentration of dose 10 percent have a response. (response is subjective could be death or increase heart rate)
EC50/ED50
Effective Concentration/Dose that
results in 50% response or response
in 50% of the population
POD
Point of Departure; Point at which
there is an effect (threshold
response) Area between NOEL and LOEL
Describe difference between chemical/drug efficacy v. potency
Efficacy: Refers to the potential maximum response that a xenobiotic can produce. Max effect.
Potency: refers to the amount of xenobiotic needed to produce a toxic effect.
You need to look at both when doing risk assessment and figuring out reference doses.
Understand the primary factors for evaluating exposure, including primary routes of exposure
Exposure: oral(gut) dermal(skin), inhalation(lungs).
Describe key factors affecting chemical/drug distribution
Toxicokinetics, effect the chemicals disruption within the body, so this is absorption, distribution, metabolism, excretion. (ADME)
Understand which factors impact individual sensitivity to chemical/drug response leading to variability in the population
Age, size, developmental stage, children, babies, pregnant, sex, genetics, individual differences, species difference.
Understand risk analysis paradigm including difference between risk assessment and risk management
Hazard x Exposure = risk
Risk assessment process of eliminating association between an exposure to a chemical or physical agent and the incidence of an adverse outcome.
Risk Management is policy and rules to reduce hazards found because of risk assessment.
Understand concept of reference dose and primary sources of uncertainty in assessing risk
Do get a reference dose that accounts for uncertainty, find the NOEL from the animal experimental data, and divide by 100 to account for animal to human extrapolation, inadequate animal data, and for sensitive populations.
Hazard Identification
Structure‐Activity Analysis
Short‐term screening tests
Animal Bioassays
Human Epidemiological Data
Exposure Assessment
Exposure Routes
Duration of Exposure
Amount of Exposure (Dose)
Exposed population(s)
Understand historical events leading up to the current computational toxicology programs in the US and EU
1976 Toxic substance control act USA, EPA required now to regulate effects of chemicals in the market for human and environmental health
1984 proposed benchmark dose methodology for dose-response assessment. Adopted by EPA
1986 first industrial implementation of high throughput screening.
1996 (FDA) Amended FQPA to develop screening program for testing potential endocrine disruptors (EDSTAC)
2003-4 EPA issues framework for computational toxicology, comp-tox research for budget.
2009 SEURAT, program to move away from animal testing in the EU.
2016 tox 21
Describe the 3R’s and how this concept supports/parallels computational toxicology approaches
The three Rs are reduce replace refine, reduce animal testing, replace with computational methods, and refine those methods to make them better and more accurate.
Describe the source‐to‐outcome continuum
prepossess that the risk assessment paradigm as a continuum of events leading from the release of a chemical in the environment to an adverse effect. Cascade of events release in environment, concentration, exposure concentrations, target organ dose, early biological effects, adverse outcome.
