Lecture 3: Factors Influencing Toxicity Flashcards
T/F: Humans and other organisms virtually never encounter one toxicant at a
time!
true! always interacting with things in mixtures
Interactions are ______ when the total amount of toxicity is the sum of the
toxicities of the compounds (2 + 2 = 4). This is usually due to the fact that
the toxicants are very similar - they have similar LD50s and/or their targets
of toxicity are the same.
additive
Interactions are ______ when the total amount of toxicity is greater
than the sum of the toxicities of the compounds (2 + 2 = 8).
synergistic
Interactions are ______ when the total amount of toxicity is less than
the sum of the toxicities of the compounds (2 + 2 = 1).
– This is the basis of antidotes!
antagonistic
T/F: antagonism is ANY level of interference between toxicants
true! there are four major types of antagonism
_____ antagonism– 2 toxicants produce opposite effects on a
physiological function
Functional
different signalling pathways affected
______ antagonism– chemical reaction between the compounds
leads to an inactivation that produces a less toxic effect.
Chemical
not through receptors
_____- antagonism– alters what happens to the toxicant in the body
Dispositional
Concentration or excretion at target tissue is affected, which affects toxicant structure
_____ antagonism– 2 toxicants bind to the same receptor and interfere with the response
Receptor
morphine/nalaxone example
T/F: Interactions can occur between toxicants and abiotic factors
true!
many aquatic organisms react to compounds in different
ways in fresh water vs. salt water
______ is when a non-toxic chemical (at the levels normally administered or encountered) makes a different toxicant even more toxic
Potentiation
example how warfarin (an anti-coagulant) is an example of potentiation
warfarin is also used as a rat poison… when in the blood, its bound by albumin (a sticky protein) which keeps the “free” concentration of warfarin in the blood low
if another low dose toxicant is administered into blood, and is also carried by albumin, the warfarin can get displaced from its pairing and can potentially reach toxic levels in the blood!
an example of a non-toxic chemical causing a different toxicant to be more toxic
________– How long it takes to remove a compound from the tissue or body of an organism
Excretion/Elimination Rate
______ gets rid of something from a tissue
Excretion
_____ gets rid of something from the body
elimination
_____ of a compound: time it takes for a concentration to be reduced by half
half-life
how does fluvoxamine (an SSRI) affect the elimination of caffeine?
fluvoxamine gives caffeine a much longer half-life in the blood, as it inhibits a protein that is involved in the metabolizing of caffeine
complex interactions can influence toxicity!
______ is where an individual becomes tolerant to different
similar toxicants because of exposure to one compound
Cross-tolerance
how do heroin users show cross-tolerance?
they have cross-tolerance to opioids, since they elicit through the same receptor… makes it very easy to overdose when mixing two things with similar cross-tolerances
the _____ of an individual to specific compounds can also influence toxicity
tolerance
_______: When a prior exposure to a toxicant alters the metabolism or physiology of the organism so that subsequent exposures to the same toxicant result in a reduced effect
tolerance
T/F: Some toxicants exist in different chemical forms
true!
T/F: Developmental stages are very important for the toxicity of a toxicant
true! age and size of organism are major factors
T/F: Some of the liver enzymes that detoxify toxicants have low expression
in human children for a few months after birth, later are gradually
expressed at higher levels
true
______– the genetic make up of an individual
Genotype
______– observable traits due to interactions between the
genotype and the environment (i.e., tolerance to a toxicant)
Phenotype
Sequence differences between individuals can be measured using
_______ to identify different
genotypes in individuals/populations/species, etc.
single nucleotide polymorphisms (SNPs)
If the protein that changed is a target of a toxicant, and the mutation causes a difference in the relative toxic effect:
– The genetic differences can be called ________
‘susceptibility factors’
If the mutation affects genes for detoxification enzymes that break down
toxicants affecting the ability to tolerate exposure:
– The genetic differences can be called ______
‘resistance factors’
why is alcohol toxic to some humans?
we normally have two aldehyde dehydrogenases that breakdown ethanol to acetate… some people have a mutation in their mitochondrial form, leading to them only having an active cytosolic form…. acetaldehyde accumulates when these people drink.. producing a toxic response
______ of a population or species influences toxicity
– a genetic basis for the ability of an organism to avoid a toxic response when exposed to a toxicant
* Usually involves mutations and evolution!
Resistance
A _______ is when a new beneficial mutation rises in frequency in a population.
* Can be very rapid when talking about insecticide resistance… since they turn over so fast!
selective sweep
______ is a big deal in “pest” management, because there’s a huge selection pressure of insecticides, meaning mutations must happen quickly and shared widely
Evolved Resistance
how does DDT work?
binds to sodium channels and keeps them open, leading to neurotoxicity
DDT resistant mosquitoes have a higher expression of detoxification enzymes… making them even more difficult to kill!
