4.1 Principles of Toxicology Flashcards
what are the two sections of the AHL toxicology laboratory
organic and inorganic
what does the organic section of the AHL toxicology laboratory test
- pesticides
- feed additives
- vitamin A and E in serum
- cholinesterase
what does the inorganic section of the AHL toxicology laboratory test
- trace minerals
- heavy metals
- iodine
- nitrate/nitrite/ammonia
what is the definition of 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
what did paracelsus come up with regarding toxicology
the notion that the dose makes the poison
how does water cause death at high enough doses
dehydrated animals have hypertonic cytoplasm -> rapidly ingesting water leads to cellular swelling through osmotic pull -> cells swell which means that tissues and organs swell -> the brain herniates out of the foramen magnum and the respiratory centers in the medulla become compromised -> death
what toxic substance do apple seeds contain
amygdalin in apple seeds, when crushed or chewed, converts to cyanide
what is the normal amount of cyanide in animal blood
< 0.5 ppm
what is the minimal lethal concentration of cyanide
3 ppm
define the following:
xenobiotic
foreign substance taken into the body
define the following:
toxin
naturally produced toxic substance
define the following:
toxicant
man-made toxic substance
define the following:
toxication
metabolic process by which the metabolized drug or chemical is more toxic than the parent drug or chemical (ex. acetaminophen -> NAPQI)
define the following:
detoxication
reduction of the toxic properties of a substance
what are the 10 areas of toxicology
- diagnostic
- developmental
- reproductive
- mechanistic
- toxicogenomics
- descriptive
- regulatory
- forensic
- environmental
- clinical
what influences exposure and toxicity (3)
- single vs multiple doses
- local vs systemic
- immediate vs delayed
how does single vs multiple doses impact exposure and toxicity of benzene
single (acute) dose: CNS depression
multiple doses (chronic): leukemia and BM toxicity
what is an example of species specificity to exposure/toxicity
bromethalin:
- cats very susceptible
- dogs less susceptible
- guinea pigs incredibly resistant (they do not metabolize bromethalin to its toxic metabolite)
what is an example of species-specificity to toxicity that has had impacts on human food regulation
saccharine in sweet n low:
causes cancer in rats because it combines with a urine protein to form crystals -> chronic irritation causes neotransformation
in humans we do not have the same crystal formation, but studies on rats led to false classification of saccharine as a carcinogen
how does susceptibility to aflatoxin differ between rats and mice
rats: very susceptible
mice: very resistant because they quickly metabolize it to less reactive forms and glucuronidation
the _________ gene codes for _________, and mutations in this gene in _________ breeds results in higher susceptibility to toxicity
multidrug resistance; P-glycoprotein; herding
what are the two multidrug resistance genes
MDR1 and ABCB1
what is P-glycoprotein, what tissues is it in and what is its role
a membrane bound transporter in the BBB and several other tissues that works by exporting drugs and toxins out of cells
what are examples of drugs that dogs with the MDR1 mutation are more susceptible to
sedatives (acepromazine, butorphanol), loperamide (the opioid), nad ivermectin
T/F only dog breeds are known to have the MDR1/ABCB1 mutation
F; cats have been seen to have it
what is an example of how developmental stage influences exposure and toxicity
thalidomide babies; severe malformations of children in utero when their mother took the drug; now used as a cancer treatment for multiple myeloma
what is an example of selective toxicity
neonicotinoid pesticides -> cause overstimulation of nAChRs (by acting as an ACh agonist)
humans are less susceptible than insects because of differences in the nAChR structure
how do we calculate therapeutic index
TD50/ED50 (half-toxic dose/half-effective dose)
describe hormesis and give an example
a dose-response effect whereby low doses of the drug are protective and high doses are toxic; example: alcohol
what are the sites of toxin exposure
skin, GI tract, respiratory tract, bite/injection site, placenta
what are the 4 opposing mechanisms that influence delivery of a toxicant to the target site
1) absorption vs presystemic elimination
2) distribution towards vs away from target
3) reabsorption vs excretion
4) toxication vs detoxication
what is toxicokinetics
movement and transformation of toxicants in the body
- absorption
- distribution
- metabolism
- excretion
what is Vd
amount of chemical in the body/concentration in plasma at equilibrium
metabolism makes ___________ molecules more _____________
hydrophobic; hydrophilic
what is toxicodynamics
what the toxicant does to the body
what are examples of toxicodynamic processes (6)
- binding and activating/blocking a receptor
- enzyme inhibition
- uncoupling oxidative phosphorylation
- lipid peroxidation
- altered cell pH
- neoantigen formation
how do we determine risk
risk = hazard x exposure
what goes into hazard identification (2)
- dose-response relationship
- association between exposure and effect
