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NRSC 333 > 8. ADME & Biomagnification > Flashcards

8. ADME & Biomagnification Flashcards

1
Q

What does ADME stand for?

A
  • Absorption
  • Distribution
  • Metabolism
  • Elimination
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2
Q

What is absorption

A

How the contaminant enters the body

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3
Q

Types of absorption (5)

A
  • Inhalation through the respiratory system
  • Dermal contact through the skin
    ○ Amphibians are sensible to it
  • Ingestion through GI system
  • Maternal transfer
    ○ Oviparous animals
  • Diffusion across lipid membranes determined in part by log KOW
    ○ Can get taken up by cells
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4
Q

What is distribution?

A

It describes how the chemical moves through the body from the site of absorption

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5
Q

Examples of distribution (2)

A
  • Often transported in blood or hemolymph
  • Often absorbed in gut and transported directly to liver (key site of metabolism)
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6
Q

What are the key target organs? (2) (of distribution)

A

Liver and brain

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7
Q

What type of molecules can cross the blood-brain barrier?

A

lipophilic molecules (polar molecules CANNOT)

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8
Q

What is metabolism (or biotransformation)?

A

The chemical breakdown of a contaminant via enzymatic reactions inside an organism

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9
Q

What is the purpose of metabolism? (3)

A
  • INCREASE polarity of the molecule (and solubility in water)
  • PROMOTE excretion
  • REDUCE toxicity
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10
Q

Can metabolism not work properly?

A

Yes, in some cases, metabolism can activate the contaminant and promote toxicity :(

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11
Q

Where does metabolism happen? (in the body)

A

Mainly in the liver

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12
Q

What is metabolism? (longer definition) (4 elements)

A
  • Body’s defence against toxic substances
  • Biological processes which transforms xenobiotics into water soluble form that can be excreted
  • Uses an army of enzymes with broad substrate specificity (not specialized)
  • One enzyme can metabolize many different things
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13
Q

What is elimination?

A

How the contaminant is removed (and how quickly)

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14
Q

Types of elimination (4)

A
  • Across gills or skin (fish and amphibians)
    ○ Applies to water soluble and lipophilic contaminants
  • Through urine or bile (in feces)
    ○ Applies to metabolites of lipophilic contaminants or water soluble contaminants
  • In breast milk or eggs
    ○ Applies to lipophilic contaminants
  • Small amount of metals eliminated through hair and nails
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15
Q

How is methylmercury aborbed? (2)

A
  • mainly through diet
  • 95% of dietary MeHg is absorbed through the GI tract
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16
Q

How is MeHg distributed and where does it accumulate?

A
  • through the bloodstream
  • it accumulates in muscle and brain (cross blood-brain barrier)
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17
Q

How is MeHg metabolized?

A

It is slowly demethylated and excreted. Half life of around 80 days

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18
Q

How is MeHg eliminated?

A

Through feces. Biomarker in hair

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19
Q

Does MeHg biomagnify?

A

Yes
- Hg0 has a low log KOW of 0.62
- MeHg has a log KOW of 2.54
- MeHg biomagnifies because it gets trapped in proteins as methylmercury cysteine

20
Q

How is TCDD (a dioxin) absorbed?

A
  • mainly through diet
  • more than 85% of dietary TCDD is absorbed through the GI tract
21
Q

How is TCDD distributed and where does it accumulate?

A
  • through bloodstream
  • accumulates in liver and fat
22
Q

How is TCDD metabolized?

A

Very slowly
it has a half life of 5-10 yeats

23
Q

How is TCDD eliminated?

A

Mainly feces

24
Q

Does TCDD biomagnify?

A

Yes
It has a log KOW of 6.8
→ when a contaminant doesn’t metabolize and has a high log KOW, it biomagnifies

25
Q

What is Phase I biotransformation?

A
  • Introduces or exposes a functional group
  • small increase in hydrophylicity
26
Q

What is Phase II biotransformation?

A
  • Conjugation (e.g. glucuronic acid)
  • large increase in hydrophilicity
27
Q

In the hitch and trailer analogy, what is Phase I of biotransformation?

A

the hitch

28
Q

In the hitch and trailer analogy, what is Phase II of biotransformation?

A

the trailer

29
Q

In the hitch and trailer analogy, what is the chemical?

A

the truck

30
Q

What are some examples of Phase I reactions? (3)

A
  • hydrolysis
  • reduction
  • oxidation
31
Q

What is hydrolysis?

A

Reaction with water that breaks a chemical bond

32
Q

What is reduction?

A

Reaction that transforms a functional group to a reduced from (usually by the addition of hydrogen)

33
Q

What is oxidation?

A

Reaction that increases the oxidation state of chemicals (usually by addition of oxygen)

34
Q

Example of a enzyme that does metabolism

A

CYP1A

35
Q

What are the 2 problems with the metabolism of DLCs by CYP1A?

A
  1. ‘Ineffective’
    * PAHs are metabolized to carcinogenic epoxides
    * Could be beneficial in the short term, but metabolite can be more toxic than parent compound
    * Most PCBs are moderately well metabolized
    * Dioxins and furans are very poor metabolized
  2. ‘Dangerous’
    * activating the AHR pathway is toxic in itself
    * e.g. AHR knockout mice are insensitive to the toxic effects of TCDD
36
Q

What can the metabolization of Benzo(a)pyrene (a PAH) result in?

A

A carcinogenic metabolite → epoxide

37
Q

Why are relatively small amounts of chocolate toxic to dogs?

A
  • This is related to the slow metabolism of a caffeine metabolite called theobromine (CYPA1 Phase I biotransformation)
  • But also the LD50 of theobromine is smaller for dogs than for humans
38
Q

How does this chocolate example apply to Risk = exposure x hazard?

A

It adds the term susceptibility to the paradigm. Susceptibility modifies the hazard term.

39
Q

What is bioconcentration?

A

Build up of contaminant in an organism to a concentration that is higher than the concentration in the media to which it is exposed

40
Q

What is bioaccumulation?

A

Build-up contaminant within the tissues of an organism (includes bioconcentration and dietary intake)

41
Q

What is biomagnification?

A

Increase in concentration of contaminants as you move up the food chain

42
Q

What is a trophic level

A

it is a position in the food web

43
Q

How does the trophic level influence biomagnification?

A

Biomagnification increases as you increase the trophic level

44
Q

What types of contaminant are more likely to biomagnify? (2 characteristics)

A
  • high log kow
  • resistant to metabolism
45
Q

Why does biomagnification increase with trophic levels?

A

Each individual takes on the contaminant burden of all of its prey, and all of its prey’s prey, etc.

46
Q

What happens if there were fewer trophic levels?

A

There would be less biomagnification.

47
Q

What is δ15N (delta n 15)

A
  • It is a measure that indicates trophic position
  • a higher δ15N = higher trophic position

NRSC 333 (23 decks)

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