Principles of Toxicology Flashcards
TOXICOLOGY
The study of the adverse effects of chemicals on living organisms.
TOXICOKINETICS
The study of the absorption, distribution, metabolism and excretion of toxins .
BIOACCUMULATION
Accumulation of toxins in tissues, especially fat, that occur over time.
BIOMAGNIFICATION
The increase in the level of a toxin which may occur as it passes up the food chain.
THRESHOLD
The level of exposure, below which there is minimal chance of an adverse effect.
LD50
The median Lethal Dose
LC50
Median lethal concentration in the environment.
LOLD
Lowest lethal dose
NOAEL
No Observable Adverse Effect Level
LOAEL
Lowest Observable Adverse Effect Level
Threshold Limit Value
Limit set for exposure to occupational toxicant - often used in workplace.
Acceptable Daily Intake
Most important measurement used for risk assessment.
Amount that can be ingested every day for life without any adverse effects
Measured as mg/kg body weight
Also known as “risk reference dose”
Usually derived from NOAEL or LOAEL with safety factors applied.
Discuss the factors affect the toxicity of a compound?
inherent toxic properties of the chemical
o dose
o duration of exposure - acute versus chronic
Effects of toxic substances can be separated on the duration of exposure:
o acute effects:
o short term or
o single exposure of a high level of toxin
o chronic effects:
o long term
o repeated exposures over long period
o usual low level exposure
o delayed effects: not apparent until some time after exposure.
o route of exposure, e.g. ingestion versus inhalation
o via GI tract passes via liver before entering circulation, but inhalation does not
o inhalation is an important route for entry of chemicals into the body, especially in industrial settings
o age, sex and species
o toxicokinetics (absorption, distribution, metabolism and excretion), e.g. water soluble versus lipid
soluble
o interactions with other chemicals, e.g. alcohol and benzodiazepines.
“ Location where effect takes place
Some toxic chemicals damage local sites or specific target organs. For example, accumulation of toxins in fat deposits or in the liver will lead to organ specific effects. Other toxic chemicals have more general systemic effects, i.e. not at point of contact but elsewhere in body.
What type of effects can a toxin have on the body?
Toxic effects can range from biochemical alterations such as inhibition or induction of an enzyme to cancers as a result of DNA damage. They may interfere with protein production, cell permeability, mitochondrial functioning etc etc. Furthermore, effects can be trivial or fatal eg birth defects, carcinogenesis.
What is the relationship between a hazard and a risk?
Hazard - ability of a substance to cause an adverse effect.
Risk - probability that a given hazard will occur under specific conditions.
What mechanisms are in place in Australia to assess and regulate potentially toxic substances?
TGA, NRA, NICNAS, Australia New Zealand Food Authority.
What type of studies are used in determining the level of toxicity of chemicals?
o epidemiological data
o attempt to correlate incidence of adverse effects with past exposures to toxic agents
o limited by accurate exposure information in many studies
o need to have a large increase in disease for effect to be noticed, e.g. correlation between birth defects and pesticide exposure
o human clinical studies
o controlled exposures in human volunteers
o only used for short term/low dose effects, e.g. effect of sulphur dioxide exposure on asthmatics
o animal studies
o used extensively
o limited by uncertainty in extrapolating to humans
o in vitro studies
o used mainly for testing mutagenic and carcinogenic potential.
In pharmacology and toxicology, the relationship between exposure and effect normally takes the form of a sigmoid curve. What does this actually mean?
The dose-response relationship is an important concept. For most substances, low doses are not toxic. As the concentration increases, it reaches the threshold level, the lowest concentration at which toxic effects are seen. Further increases in dose result in steep increases in toxicity until the point where maximum toxicity is observed. After this point, increasing the dose or exposure can have no further effect.
What other relationships may exist between the level of exposure and its effect?
For many substances (particularly carcinogens) the dose-response relationship is not sigmoidal, but may be U shaped or inverted U shaped, depending on the mechanism involved.
