Lecture 4 Part 2

Question 1

What does toxicity mean?

Answer 1

the degree to which a substance can
harm living organisms

Question 2

What are the three methods of assessing toxicity?

Answer 2

LD50, LC50, ADI

Question 3

What is LD50?

Answer 3

Lethal Dose that kills 50% of a test
population, used for ingested or injected substances

Question 4

What is LC50?

Answer 4

Lethal Concentration that kills 50% of a test
population, used for inhaled or dissolved
substances

Question 5

What is ADI?

Answer 5

Acceptable Daily Intake, used to measure
long-term exposure safety

Question 6

What are the two types of dose response relationships?

Answer 6

All or none response
Graded response

Question 7

What is an all or non response?

Answer 7

it’s the count number of dead mice in animal testing

Question 8

What is a graded response?

Answer 8

A dose-response relationship, where the effect or response to a chemical/treatment varies along a continuum.
example: measuring inhibition of enzyme activity

Question 9

What is ED50? TD50? LD50?

Answer 9

ED50 is the dose at which 50% of test animals react to a drug (is efficacy), TD50 is the dose at which 50% of test animals show a toxic response, LD50 is the dose at which 50% of test animals die (lethality)

Question 10

ED50 is used for what?

Answer 10

to find
the right dosage of a compound to relieve pain. It permits
drug effect to be anticipated by clinicians

Question 10

LD50 can be used to compare the toxic effects of various chemicals—
lower LD50 values indicate higher —————

Answer 10

toxicity, as lower amount needed to cause 50% death

Question 11

TD50 and LD50 are used by manufacturers in what?

Answer 11

to recommend dose ranges for safe prescribing

Question 12

LD50 is a measure of what type of toxicity?

Answer 12

measure of acute toxicity, meaning it tells us how much of a substance can cause death after a single or short-term exposure

Question 13

What is LD01 and LD100?

Answer 13

LD01 is the lethal dose for 1% of the test popln, LD100 is the lethal does for 100% of the test popln

Question 14

What are the key differences between LD50 and LC50?

Answer 14

LC 50 Concentration-based, for —–gaseous——– or ——-dissolved—– substances.
* LD50: Dose-based, for —-injected——— or —–injested——- substances

Question 15

What is LD50 measured in?

Answer 15

mg/kg of body weight

Question 16

What are the classifications of LD50 based on dose ranges?

Answer 16

LD50 Classification
< 5 mg/kg Extremely toxic
5-50 mg/kg Highly toxic
50-500 mg/kg Moderately toxic
500-5,000 mg/kg Slightly toxic
5,000-15,000 mg/kg Practically non-toxic
> 15,000 mg/kg Relatively harmless

Question 17

What does LD50 depend on?

Answer 17

mode of entry, whether its: oral, subcutaneous, intramuscular, intraperitoneal, intravenous

Question 18

Will all mammals have the same response to a substance?

Answer 18

No, for ex: paracetamol (tylenol) rapidly induces liver damage to cats (not as rapidly in humans or rats)

Question 19

What is NOAEL?

Answer 19

The dose below which none of the test
animals are affected

Question 20

What are non-threshold effects versus threshold effects?

Answer 20

Non-threshold effects show there’s a theoretical risk at any level of intake
threshold effects mean there’s a low level of intake that doesn’t have risk

Question 21

What is mutagenicity? genotoxicity?

Answer 21

are damages to genes/dna, have non-threshold effects

Question 22

What is ADI?

Answer 22

Is the acceptable daily intake, The amount of a specific compound a person could eat
every day over their entire life without any negative health
effects

Question 23

How do you estimate ADI?

Answer 23

divide the NOAEL by a safety factor, typically 10, 100, 1000, but 100 is typically used

Question 24

What is selective toxicity?

Answer 24

Differences in susceptibility to toxic effects between:
different species of animal
different cells

Question 25

What are the reasons for selective toxicity?

Answer 25

Metabolism and Biotransformation (e.g., presence of receptors)
* Absorption, Distribution, Metabolism, and Excretion (ADME)
* Target Organ Sensitivity
* Dosing

Question 26

What examples of substances that selectively toxic?

Answer 26

rodenticide norbormide- active against rats because they have a receptor in smooth
muscle that humans lack
penicillin- interferes with synthesis
of cell wall of bacteria

Question 27

What are additive, synergistic, and antagonistic effects?

Answer 27

additive: The combined effect of two chemicals is equal to the sum
of their individual effects.
e.g., aspirin or acetaminophen
synergistic: The combined effect of two chemicals is greater than the
sum of their individual effects
e.g., alcohol and pain killers
Antagonistic: The combined effect of two chemicals is less than the
sum of their individual effects.
▪ e.g., birth control pills and certain antibiotics

Question 28

What are the four alternative to animal testing found?

Answer 28

zebrafish, in vitro models, organoids and organ on a chip, computer modelling

Question 29

What is the 3Rs principle?

Answer 29

Replacement, Reduction, Refinement

Question 30

What are the benefits of using zebrafish?

Answer 30

1. Cost-effective and efficient models.
2. Small, produce many offspring, transparent, and share many genetic similarities with mammals.
3. New applications in neurological, cardiovascular, and developmental research.
4. well suited for embryonic studies as they apply optical clarity