Factors Influencing Toxicity Flashcards
type of response depends on many factors
- route of exposure
- endpoints we measure
- duration of study
- properties of the compound
- single compound vs mixture
- half-life of the compound
- excretion rate
- tolerance
- resistance
- genetics
toxicants interact in a mixture
- additive
- synergistic
- antagonistic
additive
- the total amount of toxicity is the sum of the toxicants of the compounds (2+2=4)
- toxins are very similar (same LD50 or targets of toxicity)
synergistic
total amount of toxicity is greater than the sum of the toxicities (2+2=8)
antagonistic
total amount of toxicity is less than the sum of the toxicities of the compound (2+2=1)
agonist vs antagonist
- activates the receptor
- deactivates the receptor
interactions can occur between toxicants and abiotic factors
react to compounds in different ways in fresh water vs salt water
potentiation
when a non-toxic chemical makes a different toxicant even more toxic
toxicants exist in different chemical forms
forms can be either modified by metabolism by the individual or by environment-driven chemical reactions
Karen Wetterhahn
expert in metal toxicity
genotype
the genetic make up of an individual
phenotype
observable traits due to interactions between the genotype and the environment
genetics of the organism
-organisms from the same species share the same compliment of genes that collectively encode all the proteins
mutation
- exchanging one nucleotide with another
- resistance evolves
- explain some variation in responses across a species
polymorphisms
differences in the DNA sequences between individuals
single nucleotide polymorphisms (SNPs)
- tell the difference between different genotypes in individuals
- can lead to differences in the amino acid sequence of the encoded proteins, changing how the protein functions
susceptibility factors
protein that changed in a target of a toxicant, then the difference in function can affect the severity of the relative toxic effect
resistance factors
genes encode enzymes that break down toxicants
genome duplication events
- facilitate the evolution of resistance or tolerance to a toxicant
- random genome duplication can change the policy level of a species
- because there is an original copy that still functions in its normal way
isoforms
- novel function can evolve in the extra copies of the genes
- tend to function in a tissue specific way
age and size
- toxicant can have a greater effect at one of these stages
- smaller=easier to receive a toxic dose
excretion/elimination rate
how long it takes to remove a compound from the tissue (excretion) or body of an organism (elimination)
half-life
time it takes for a concentration to be reduced by half
chronic or repeated doses can eventually reach toxic levels, depending on…
- the dose at each step of repeated exposure
- how quickly the toxicant is metabolized or excreted
tolerance
-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
cross-tolerance
an individual becomes tolerant to different similar toxicants because of exposure to one compound
resistance of a population or a species
- a genetic basis for the ability of an organism to avoid a toxic response when exposed to a toxicant
- mutations and evolution
resistance mechanisms include
- selection for a resistance factor gene already in a population
- selection for a new mutation in a resistance factor gene
- multiple copies of a gene already in the organism arise
- a brand new gene picked up from the environment or another organism
- genetically engineered into a species
selective sweep
- a new beneficial mutation rises in frequency in a population
- insecticide resistance or vaccines
Insect resistance
-become resistant to compounds due to the huge selection pressure of using insecticides
