toxicology Flashcards
What trends do we see in chemical production in the USA?
increase in chemical production
toxicology
the study of the adverse effects of chemical, physical or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such adverse effects.
chemical hazard regulations
The Toxic Substances Control Act of 1976
The Toxic Substances Control Act of 1976
authorized the EPA to both assess new chemicals before they enter the marketplace and to review chemicals already on the market.
When the law was enacted, thousands of chemicals already being used were grandfathered in and accepted as just being okay in commerce
EPA has taken actions to regulate exposure to about 3,500 of 32,000 new HPV (High Production Volume - >1,000,000 pounds produced each year) chemicals submitted for review since TSCA was enacted
Xenobiotic
chemical substances foreign to the biologic system. Incl natural occurring substances, drugs, etc.
toxin
a toxic substance made by living organisms
toxicant
toxic substances that are man made
Goal of toxicology
To understand the causal relationships between toxicant exposure and adverse human health effects
Experimental Methods of toxicology
Highly controlled experiments, usually in a laboratory setting, typically using animals
Epidemiological Methods of toxicology
Observations on uncontrolled populations, usually in the natural environment
toxicology basic understanding:
Even innocuous (non-harmful) substances can become toxic in high doses
High O2 can lead to O2 intoxication
Too much water can cause osmotic imbalance or brain damage
Dose-response relationship
Type of correlative relationship between “the characteristics of exposure to a chemical and the spectrum of effects caused by the chemical”
Dose-response Curve
type of graph
Used to describe the effect of exposure to a chemical or toxic substance upon an organism such as an experimental animal
Different curves used for individuals v populations
how do we measure toxicity
The classical measure of acute toxicity is the LD50
LD50: Lethal dose that kills 50% of the study population.
Dosage is measured in weight of toxicant per body weight of subject, often as mg toxicant/kg body weight.
Drug action is measured by the ED50
ED50: Effective dose that produces the desired effect in 50% of the population.
problem with animal studies
Does Not stimulate the real world
What we learn is very specific
Does give us some ideas, inclinations, and directions to follow in the future studies
Usually high dose exposure requiring extrapolation
acute toxicity
single exposure to a toxicant
poisoning
usually life threatening effect
diagnoses and treatments or antidotes available
subacute/chronic toxcity
prolonged exposure to a toxicant
no immediate effect but could be life-threatening in the long term
organ system effects and cancer are endpoints
usually difficult to diagnose and treat
difficult to distinguish from other influences
risk assessment paradigm
Hazard assessment
Exposure assessment
Risk assessment
Risk Management
Hazard assessment
animal studies
Exposure assessment
field studies
Risk assessment
hazard x exposure, extrapolation to humans, safety factors
Risk Management
depends on context, risk-benefit analysis
what we know about chemical mixtures
We are not exposed to things in a vacuum
Most difficult challenge yet, most common situation
3 joint interactions of chemical mixtures
antagonism
additivity
synergism
antagonism chemical mixtures
response is less than expected
physiological –> severe drop in blood pressure resulting from barbituate overdose can be reversed by administering vasopressors
chemical –> reduce mercury toxicity by chelating ions with dimercaprol
disposition –> swallowed poison is absorbed by charcol in the stomach
receptor –> carbon monoxide poisoning is treated with oxygen to displace carbon monoxide hemoglobin receptors
additivity chemical mixtures
the response as expected
dose(exposure) and response (effect)
synergism chemical mixtures
the response is greater than expected
cosynergism –> two agents enhance the toxicity of each other
potentiation –> only one agent affects the toxicity of the other with no toxicity itself
coalitive –> two agents with no observable toxicity effect
individual dose-response graph
demonstrates the response to a chemical as exposure increases –> assumes a one time exposure and a graded increasing response as a dose of the substance increases
population dose-response graph
demonstrated observed outcomes in a population –> the relationship of observed responses or outcomes in a population to varying levels of beneficial or harmful agents
