Toxicokinetics

Question 1

what are there three types of accumulation and frequencies of exposure

Answer 1

1. acute
2. subchronic
3. chronic

Question 2

what are the three assumptions of descriptive animal toxicity testing

Answer 2

1. biological response in animals is representative of humans
2. exposure to high doses necessary and valid
3. results from new comics technology likely still requires verification

Question 3

what are the five goals of astute animal testing

Answer 3

1. provide an estimate of the intrinsic toxicity of the substance
2. provide information on target organs and other clinical manifestations
3. identify species differences and susceptible species
4. establish the reversibility of the toxic response
5. provide information that will guide dose selection for longer-term studies

Question 4

what is genomics

Answer 4

DNA coding for mRNAs and microRNAs

Question 5

what is epigenetics

Answer 5

DNA methylation or histone deacetylation

Question 6

what is transcriptomics

Answer 6

all mature mRNA in a cell

Question 7

what is proteomics

Answer 7

proteins and their post-translational modification

Question 8

what is metabonomics

Answer 8

small molecule substrates for metabolism

Question 9

what does ADME stand for

Answer 9

Absorption
Distribution
Metabolism
Elimination

Question 10

describe passive transport of toxicants

Answer 10

• small hydrophilic molecules can cross membranes via aqueous pores
• large molecules cross phospholipid bilayer in nonionized state
• down conc gradient

Question 11

regarding passive transport, higher LogP means what

Answer 11

higher permeability

Question 12

what is the most common route for accidental poisoning

Answer 12

absorption

- sublingual and rectal

Question 13

describe volatility of ionized/ non ionizes gasses and vapors

Answer 13

ionized=low volatility

Question 14

what is the rate-limiting barrier of skin

Answer 14

stratum corneum

Question 15

why is stratum corneum the rate limiting barrier of skin

Answer 15

made of densely packed keratinized cells that are metabolically inactive

Question 16

absoprtion through skin depends on? (5 things)

Answer 16

1. integrity of stratum corneum
2. hydration state of stratum corneum
3. temperature
4. solvents as carriers
5. molecular size

Question 17

what does the toxicant moving out of capillary bed into cells depend on

Answer 17

water solubility
lipid solubility
active transport

Question 18

example of storage of toxicant at the site of action

Answer 18

carbon monoxide binding to hemoglobin

Question 19

example of storage of toxicant at another site

Answer 19

lead storage in bone, but toxic in soft tissues

Question 20

what are the four main sites of toxicant storage

Answer 20

1. plasma proteins
2. liver and kidney
3. fat
4. bone

Question 21

describe toxicant storage in liver and kidney

Answer 21

• major storage sites
• metallothionine binds to essential and toxic metals
• liver sequesters
• kidney forms a toxic conjugate

Question 22

describe toxicant storage in fat

Answer 22

• long term storage of lipid-soluble ocmpounds

- polycyclic aromatic hydrocarbons, DDT

Question 23

describe toxicant storage in bone

Answer 23

• fluoride, lead, strontium

Question 24

describe elimination through kidney and urine

Answer 24

• glomerulus filters
• once filtered, compound may be excreted via urine or reabsorbed
• respsorption according to same rules from GI tract

Question 25

describe phenobarbital poisoning in the kidney

Answer 25

• Phenobarbital is a weak acid
• treat toxicity with sodium bicarbonate to buffer
• increase urine pH will increase proportion of ionized phenobarbital