Intro and Principles

Question 1

Why is Paracelsus referred to as the father of toxicology?

Answer 1

• advocated focus on toxicon (primary toxic agent)
• dose-response relationship
• responses to chemical
• distinguish between therapeutic and toxic properties based on dose
• specificity of therapeutic and toxic effects of chemicals

Question 2

Differentiate between toxin and toxicant

Answer 2

• toxin: poison produced by living organims
• toxicant: man made poisonous substance

Question 3

Define xenobiotic

Answer 3

• any substance foreign to an organism
• any compound not found within the normal pathways of a biological system

Question 4

Explain the exponential growth of toxicology over the last few decades.

Answer 4

• multidisciplinary: grown and prospered by borrowing form other disciplines
• continuous, emergent, interactive
• grow in response to regulatory needs or perceived risk
  
  • public mistrust of chemicals

Question 5

Define LD50.

Answer 5

• dose lethal to 50% of exposed animals

Question 6

Provide the limitations of LD50.

Answer 6

• does not reflect full spectrum of toxicity
  
  • chemcials with low acute toxicity may be carcinogenic or teratogenic
• tells nothing about nature or severity of effects in survivors
• specific to exposure conditions
  
  • species, age, sex, size, route, duration, environment, physiology

Question 7

What is a dose-response relationship?

Answer 7

• correlative relationship that brings together the characteristics of exposure and the spectrum of effects

Question 8

List the fundamental assumptions of the dose-response relationship.

Answer 8

• response is due to the chemical adminsitered of the toxicant to which the animal is exposed
• the chemical interacts with a molecular or receptor site to produce a response
• the degree of response is correlated with concentration of toxicant at receptor sites
• concentration of toxicant at receptor sites is related to dose of toxicant received
• methods exist to measure and express toxic effect

Question 9

Differentiate between toxicokinetics and toxicodynamics.

Answer 9

• toxicokinetics: absorption, distribution, metabolism, excretion
  
  • how a substance gets into the body and what happens to it in the body
• toxicodynamics: interaction of toxicant with target site

Question 10

What conditions need to be met for toxicosis to occur?

Answer 10

• toxicity occurs when a xenobiotic or tis metabolite reaches appropriate sites in the body at adequate concentrations and for an adequate length of time
  
  • rate of uptake and distribution must exceed rate of elimination
  • right place at high enough concentration for long enough time
  • exposure does not equal toxicity

Question 11

Toxic responses occur over a wide range of biological organizations. Provide the differences in the responses that occur at the extreme ends of biological organization with respect to: response time, importance, cause and effect linkage difficulty

Answer 11

• lower levels explain mechanism
• higher levels provide significance
• as you go from lower levels to higher levels
  
  • increasing response time
  • increasing difficulty of linkage to specific toxicant
  • increasing importance

Question 12

Toxic responses at all levels of biological organization are important. True/false? Explain.

Answer 12

• true, all levels are connected so if it affects one level it is going to affect them all

Question 13

Differentiate between quantal and graded dose-response.

Answer 13

• quantal dose response
  
  • distribution of responses to differnet doses in a population of organisms
    
    • all or nothing – either responders or non responders
    • relates dose to frequency of responses
  • prediction of proportion of a population that responds in a specified manner to doses of a toxicant
  • within a population, the majority will respond to a given toxicant dose
    
    • some more sensitive, some less sensitive
    • bell curve – normal distribution
• graded dose response
  
  • response of a biological system to varying doses of a chemical
    
    • continuous and gradual – from minimal detectable to maximal response
    • relates dose to intensity of response
  • EC50 – half the maximal effective concentration
  • closer to left = more potent

Question 14

Draw a dose-response curve for a trace nutrient such copper, zinc, or a vitamin.

Answer 14

• both low and high concentrations are associated with adverse effects

Question 15

Define hormesis.

Answer 15

• a stimulatory effect exhibited with exposure to low, subinhibitory levels of some toxicant or physical agent
  
  • low dose = stimulation
  • high dose = inhibition

Question 16

Define non monotonic dose-response

Answer 16

• dose response relationships in which the direction of the response changes with increasing or decreasing dose
  
  • response increases at low dose, but then decreases at high dose

Question 17

Differentiate between hormetic, nonmonotonic and trace nutrient dose response curves.

Answer 17

• hormesis: stimulates then inhibits as dose increases
• nonmomotonic: response increases then decreases as dose increases (or vise versa)
• trace nutrient: adverse effects then homeostasis then adverse effects as dose increases

Question 18

Define threshold dose.

Answer 18

• the minimum dose of a toxicant at which detectable effects are observed
  
  • falls between expermentally NOEL and LOEL

Question 19

Define ED50, LC50

Answer 19

• ED50: half maximal effective concentration
  
  • amount of material required to provide a specific effect i n50% of population under specified conditions (quantal D-R)
• LC50: concnetration where half the population dies (lethal)
  
  • dose that causes death in 50% of the animals

Question 20

What do NOAEL and LOAEL stand for?

Answer 20

• NOAEL: no observed adverse effect level
  
  • highest dose at which a significant adverse effect is not found
• LOAEL: lowest observed adverse effect level
  
  • lowest dose at which a significant adverse effect is found

Question 21

Arrange MLD, LD50, LOEL, MTD and NOEL in ascending order.

Answer 21

• LD50: lethal dose 50%
  
  • dose at which half the population dies
• MLD: minimum lethal dose
  
  • lowest amount of a substance that, when introduced into the body, cases death to individuals under defined conditions
• MTD: minimum toxic dose
  
  • lowest dose of a substance at which you expect to seed clinical signs
• LOEL: lowest observed effect level
  
  • lowest dose at which a significant effect is found
• NOEL: no observed effect level
  
  • highest dose at which a significant effect is not found

Question 22

Define idiosyncrasy, bioavailability

Answer 22

• idiosyncrasy: genetically determined abnormal reactivity to a chemical
  
  • extreme sensitivity to low doses or extreme insensitivity to high doses
• bioavailability: extent to which a substance is absorbed and circulated in the body