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Potency, Exposure and Risk
General Types of Toxic Effects
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Graded Versus Quantal Toxic Responses
Potency Versus Efficacy?
Some Important Potency Metrics
Reference Dose
Response to Essential Chemicals
Is Knowing Potency Enough?
Some Conclusions
Chemicals in the Environment
General Types of Toxic Effects
Normal effects – effects that are predictable based upon the physical-chemical properties of the chemical agent.
Abnormal effects – effects that are predictable based upon the immunological properties of the organism.
Normal effects are relatively easy to manage.
Abnormal effects are very difficult to manage.
Time as a Determinant of Toxic Actions
Acute effects – those that arise within 96 h to one week after the start of chemical exposure.
Sub-chronic effects – those that arise within one week to one year after the start of chemical exposure.
Chronic effects – those that arise after more than one year after the start of chemical exposure.
Types of exposure – continuous, pulsed or one-time in nature.
Graded Versus Quantal Responses
Graded Responses – those measured in single individuals over time with increasing dose. Commonly used in pharmacology.
Quantal Responses – those measured in populations over time with increasing dose. Commonly used in toxicology.
Potency Versus Efficacy
Potency – the amount of chemical needed to cause an effect. The more chemical = the less potent!
Efficacy – the mechanism by which a chemical acts.
Potency is a Population Metric
Potency is Determined via Bioassay
Dose-Response Measurement
The Cumulative Response Curve
The Log Dose-Response Curve
Factors Important in Determining Toxicity
Chemical type
Organism type (species, sex, age, etc.)
Time (from first exposure to endpoint measurement)
Route of exposure (oral, dermal, gills, lungs, etc.)
Measured potency values reflect ONLY the conditions of the test they were derived from.
Some Important Potency Metrics
LD50 = the lethal dose for 50% of a population
TD50 = the sublethal (toxic) dose for 50% of a population.
ED50 = the therapeutic (effective) dose for 50% of a population.
NOEL = no observable effect level, or the highest dose that does not produce an observable effect (threshold).
For aquatic organisms, exposure concentrations are commonly used – LC50, TC50, EC50, and NOEC.
Determination of Relative Potency
I. Potency May be Measured for Many Effects
A Relative Ranking System for Chemicals
Margin of Safety
Margin of Safety – What it Means
Necessary to determine for drugs.
Commonly measured via the therapeutic index.
Large TI value = over-the-counter drugs.
Moderate TI value = prescription drugs.
Small TI values = physician-administered drugs.
Therapeutic Index
Calculation can be liberal or conservative.
Liberal – TI = TD50 / ED50
Conservative – TI = TD1 / ED99
The conservative approach is usually most protective.
Threshold Dose – More Important than Potency?
Threshold Versus Non-Threshold
Threshold chemicals require a certain amount before a toxic effect can occur.
Non-threshold chemicals in theory can cause a toxic effect with as little as one molecule (one-hit theory of carcinogens).
Think of the analogy of robbing Fort Knox!
The Reference Dose
The reference dose (RFD) was once referred to as the acceptable daily intake (ADI).
The RFD is generally set at some dose below the threshold.
The RFD is set using safety factors (SFs).
RFD = NOEL / 1 + SFs
Response to Essential Chemicals
Is Knowing Potency Enough?
Think Risk Instead of Potency!!
Chemical risk – The inherent probability that a chemical exposure will result in an adverse effect.
Risk is not only based on the potency of a chemical, but also on your exposure to it – moon rocks!
Risk = exposure / LD50
If you have no chance of being exposed to a toxic agent, no matter how potent it is it poses no risk to you!
Some Conclusions
Chemical effects can be normal or abnormal.
Effects can be acute, sub-chronic, or chronic in nature.
Effects are characterized by median effect levels.
Potency is characterized by ED, TD, or LD metrics.
Margin of safety determines use of drugs.
Probably all chemicals act in a threshold fashion.
RFD designates safe levels of chemicals for use.
Think of chemicals in terms of risk, not merely potency.
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Concentration (%)
Survival (%)
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