Toxicology Flashcards
Toxicology- Def.
Study of poisons/toxicants and their occurrence, effects, properties, regulation and how to detect
Goals of Toxicology
Toxicant Identification, Intoxication Prevention, Mode of Action, Intoxication Management
Intoxication Prevention
Eliminate, Minimize Exposure, Maximize Tolerance
Mode of Action
Target Organs, Cells Affected, Molecular Site
Intoxication Management
Regulate Dose, Treatment
Does toxicology intersect with different fields of study
Yes: immunology, nutrition, chemistry
What is nutritional toxicology?
a subfield of toxicology that targets the study of poisons delivery through oral exposure
What are the routes of oral exposure?
water, diet, accidental ingestion
Nutritional Toxicology also looks at:
effects on nutrient utilization, effects on production/health, mitigation of toxicant effects
Challenges of Nutritional Toxicology
Route of Exposure: Orally
Why is Oral exposure challenging?
diet complexity
What are the general principles of toxicology?
Factors Affecting Toxicity, Doses Response Concept, Phases of Toxicity, Risk Assessment
What are the factors affecting Toxicity?
exposure, dose, rate/extent of absorption, target species, sex, physiological status, nutritional status, elimination, distribution, bioaccumulation
What is bioaccumulation?
toxicant accumulating in bones, fat, or the body: happens often when exposed during growth
usually occurs over multiple exposures and often due to low rate of elimination
What are the general toxicant properties?
qualitative and quantitative
What are qualitative toxicant properties?
mode/mechanism of action (carcinogen, vasoconstrictor), primary target tissues (hepatotoxin, neurotoxin)
What is the Central Concept of Toxicology?
The dose response
What is the dose response?
All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy. - Paracelsus
Dose Response Relationship
Response Due to Chemical, Response changes with dose, method for response
What does response changing with dose affect?
molecular target site, target site dose changes with change in dose administered, response related to target site dose
What are the two types of Dose Responses?
Graded Dose Response, Quantal Dose Response
What is Graded Dose Response?
dose response elicited by an INDIVIDUAL animal; characterized by dose related changes in the severity of toxic response (weight loss, decreased production)
What is Quantal Dose Response?
dose response typically utilized when studying population to a toxicant response
ALL or NONE
characterized by dose related changes in the number of individuals of a population responding (death rate, pregnancy rate)
Potency vs Efficacy
straight line- more effective
curved line- more potent
Potency
the strength of a toxicant at a given dose
Dose Response may affect:
tolerance
What is tolerance?
state of decreased responsiveness to toxic effect of a chemical as result of a prior exposure to the chemical
What is tolerance?
state of decreased responsiveness to toxic effect of a chemical as result of a prior exposure to the chemical
What are the two types of tolerance?
Dispositional, Reduced Responsiveness
What is dispositional tolerance?
decrease in amount of toxicant reaching target site
What is reduced responsiveness?
target tissue less responsive to toxicant: metabolism, toxicant ejection, molecular site become refractory to the toxicant
What is the threshold dose?
dose below which no adverse effect occurs
What is the region of no effect?
the normal range, often termed the therapeutic range
What must happen for a chemical to elicit a toxic effect in the animal?
exposure to toxicant, absorption of toxicant, elicit action at molecular site
What are the phases of toxicity?
exposure, toxicokinetic, toxicodynamic
What does the phase toxicokinetic in phases of toxicity included?
absorption (active, passive, facilitated), distribution, metabolism (biotransformation), elimination
What does the phase toxicodynamic in phases of toxicity include?
toxic action
What is the rate of elimination?
how long it takes a substance to be eliminated (urinary, feces, metabolic)
What does rate of elimination effect?
whether animal reaches toxic level in circulation and/or how long they will stay at toxic level
What are the two phases of biotransformation?
Phase I (cytochrome P-450), Phase II (glucuronidation)
What is Phase I of Biotransformation?
introduce a polar group (OH, NH, SH, COOH) into a compound
What does introducing a polar group do?
increases water solubility
Examples of Phase I of biotransformation
Cytochrome P450: mitochondrial, microsomal
FAD containing monooxygenase: microsomal
Nonmicrosomal oxidation systems: alcohol and aldehyde dehydrogenases
What is Phase II of biotransformation?
conjugation reactions: sugars and amino acids are attached to chemicals to increase water solubility
Examples of Phase II biotransformation
glucuronidation, sulfonation, amino acid
Can Phase I biotransformation prepare substance for Phase II?
yes
First Order Elimination
rate DEPENDENT on plasma level
Half-life INDEPENDENT of plasma level
Zero Oder Elimination
Rate INDEPENDENT of plasma level
Half-life DEPENDENT on plasma level
What order of elimination is saturable?
Zero Order
What order of elimination has a curved line and which one as a straight line?
Curved: First order
Straight: Zero Order
Can a toxicant shift from zero order to first order?
Yes
What are the types of Toxic Modes of Action?
Reversible interactions, Irreversible covalent interaction, Physical sequestration (accumulation in bone, fat)
How does toxicant elect a response?
cell maintenance, cell regulation
What is Xylitol?
5 carbon sugar alcohol sweating agent that is naturally occurring
Xylitol may also function as a?
hapten (allergic reaction possible)
Where can Xylitol in nature be found?
animal, plant (beechwood), fungal metabolite
Xylitol is Derived from?
Xylose via reduction of carbonyl group to an alcohol
True or False: Xylitol can cause Prevention of dental carries in humans
True
What are human treat that have xylitol?
gum, candy, cookies, peanut butter (not all)
What are some alternative names of Xylitol?
birch sugar, sylvite, zylatol, anhydroxylitol
What is the toxicant action of xylitol?
xylitol is rapidly converted to glucose causing rapid insulin release which causes a rapid drop in blood glucose
Xylitol leads to what and how quickly:
hypoglycemia, within 30 minutes and last as long as 28 hrs
Why does Xylitol cause rapid glucose drop?
may have a direct effect on beta cells in pancreas
Xylitol can lead to what:
Liver insufficiency/failure: only occurs in some dogs, mechanism is unknown (perhaps depletion of ATP in liver)
What are common clinical signs of Xylitol Poisoning?
vomiting, lethargy, diarrhea, ataxia, seizure, restlessness, reduced food intake
