Introductory Toxicology

Question 1

Factors Effecting Toxicity

Answer 1

Disposition,
Chemical properties
Other Chemicals (effect on ADME)
Individual Characteristics

Question 2

Disposition Effect on Toxicity

Answer 2

Pharmacokinetics - absorption, distribution, metabolism, excretion

Question 3

Chemical Properties effect on Toxicity

Answer 3

Molecular weight, e.g. X>500 Daltons can’t be absorbed through skin.

Lipid solubility. More lipid soluble crosses membrane easier.

Plasma binding, prevents toxicant function

Question 4

Individual Characteristics Effecting Toxicity

Answer 4

-Age, [children easier skin absorption] [Elderly liver worse]
-Gender
- Weight (adipose storage)
- State of health
- Genetics (polymorphisms susceptibility)

Question 5

Exposure Factors

Answer 5

Route
Intensity
Frequency
Duration

Question 6

Routes of Exposure

Answer 6

Inhalation,
Ingestion
Dermal absorption
Injection (IV 100% bioavailable)

Question 7

Threshold Dose

Answer 7

Below there is no effect. First point response occurs.

[Genotoxic compounds no threshold, any dose, long window of potential effect]

Question 8

No observed adverse effect level (NOAEL)

Answer 8

Highest tested dose where there is no response.

Question 9

Lowest observed adverse effect level (LOAEL)

Answer 9

Lowest tested dose where there is a response.

Question 10

Safest Human Dose (SHD)

Answer 10

(Threshold dose (mg/kg) x 70kg) /safety factor

safety factor example: rate of skin penetration of chemical

Question 11

TD50

Answer 11

Dose where toxicity observed in 50% of population [Quantal] or dose where 50% of maximal toxicity observed [graded/continuous]

Question 12

Monotonic Dose-response Relationship

Answer 12

Standard as dose increases response increases until max response reached.

(Response could be quantal (yes or no) or graded (change in blood pressure)

Question 13

Therapeutic Index

Answer 13

Ratio between effective dose in 50% of population and toxic dose in 50% of population. [Gap between ED50 and TD50]

Bigger the better.

Question 14

Margin of Safety

Answer 14

Ratio between the amount of drug that is toxic to 1% of the population and the amount of drug that is effective in
99% of the population

Question 15

Non-Monotonic Dose Response Relationship

Answer 15

Increase in dose does not mean increase in response (toxicity)

-toxicant activates mechanisms that act in opposition. (endocrine based mechanism commonly sees)

Point of inflection slope of curve changes direction.

Question 16

Hormesis

Answer 16

Beneficial at low doses, toxic effects occur at higher doses (vitamins)

Question 17

Low Dose Effects

Answer 17

Biological change occurring in the range of typical human exposures or at doses lower than those typically used in standard testing protocols.