Unit 2 Mechanism of Toxicity and Toxicokinetics

Question 1

Immunologically mediated adverse reaction to a chemical

Answer 1

Chemical Allergy

Question 2

Situation when pre-exposure of chemical is required to produce
toxic effect

Answer 2

• Allergic reaction
• Sensitization reaction

Question 3

refers to a genetically determined abnormal reactivity to a chemical

Answer 3

Chemical idiosyncrasy

Question 4

Order of frequency of involvement in systemic toxicity

Answer 4

1. CNS
2. Circulatory system
3. Blood and hematopoietic system
4. Visceral organs (liver, kidney, lungs and skin)

Question 5

Sources of Ultimate toxicant include:

Answer 5

• Parent compound from a biological source
• Metabolite
• Reactive Oxygen or Nitrogen Species produced by biotransformation reactions.

Question 6

he intensity of the toxic effect depends on the concentration and persistence of the __________

Answer 6

ultimate toxicant

Question 7

The_____________ is responsible for causing the toxicity

Answer 7

ultimate toxicant

Question 8

Mechanisms Facilitating Distribution to a target

Answer 8

✔Porosity of the Capillary Endothelium
✔Specialized Transport across the Plasma membrane
✔Accumulation in cell organelles
✔Reversible Intracellular binding

Question 9

Mechanisms Opposing distribution to a target

Answer 9

✔Binding to Plasma Proteins
✔Specialized Barriers
✔Distribution to Storage sites
✔Association with intracellular Binding Proteins
✔Export from Cells

Question 10

possesses very long duration due to inability of effective elimination. This results to repeated exposure.

Answer 10

Highly Lipophilic Compounds

Question 11

Excretion for Highly Lipophilic Compounds

Answer 11

• From the mammary gland (breast milk)
• Bile
• Intestinal lumen from blood

Question 12

EXcretion for Volatile, nonreactive toxicants (gas and volatile liquids)

Answer 12

Pulmonary Capillaries and alveoli

Question 13

Reabsorption happnes wherein the product can go back again into the system via

Answer 13

tubular fluid reabsorption

Question 14

Possible production of Toxication (metabolic activation)

Answer 14

• Electrophiles
• Free Radicals
• Nucleophiles
• RedOx active reactants

Question 15

Different mechanisms of detoxification

Answer 15

⮚Detoxification of Toxicants with no Functional Group
⮚Detoxification of Nucleophiles
⮚Detoxification of Electrophiles
⮚Detoxification of Free Radicals
⮚Detoxification of Protein Toxins

Question 16

Detoxification Process and Enzyme of Toxicants with no Functional Group

Answer 16

Hydroxylation/c arboxylation Conjugation - CYP 450 Tranferase

Question 17

Detoxification Process and Enzyme of Nucleophiles

Answer 17

Conjugation, Tranferases

Question 18

Detoxification Process and Enzyme of Electrophiles

Answer 18

Conjugation, Glutathione S transferase

Question 19

Detoxification Process and Enzyme of Free Radicals

Answer 19

ReDoX, Superoxide dismutase Glutathione peroxidase Catalase

Question 20

Detoxification Process and Enzyme of Protein Toxins

Answer 20

Reduction, Thioredexin

Question 21

Reasons for Failed Detoxification:

Answer 21

1. Toxicant overwhelms the detoxification process
2. Reactive toxicant inactivates a detoxifying agent enzyme
3. Detoxification is reversed after transfer to other tissues
4. Harmful by products are produced by the detoxification process