L4: Contaminant Uptake, Biotransformation, Detoxification & Elimination

Question 1

E-waste

Answer 1

20-50 M tonnes per year of end-of life electronics
Uncontrolled disposal and recycling of e-waste in developing countries
Source of lead, cadmium, mercury, phthalates, PBDEs, PCBs, PCDD/Fs and other POPs
Ppl working at e-waste facilities have highest exposure
Elevated PCBs and PBDEs in birds near e-waste

Question 2

Site of:
action
metabolism
storage
excretion

Answer 2

Site of action: interacts w molecule (pr/DNA) or structure to have toxicity
Site of metabolism: where enzymes metabolize contaminants, usually lead to detoxification
Site of storage: exists in inert state, sequestered (no toxicity)
Site of excretion: loss from body of either original contaminant or biotransformation product

Question 3

3 main routes of contaminants into cells

Answer 3

Always starts w cell surface

1) Lipid: passage thru lipid bilayer of membrane, hydrophobic contaminants
2) Aqueous: membrane transport pr (channel/carrier pr) transfer hydrophilic contaminants (function of these pr can be affected by contaminants)
3) Endocytosis

Question 4

Mechanisms of uptake into cells

Answer 4

Diffusion thru channel (gated or not)–lipophobic contaminants
Diffusion across lipid (w gradient) –lipophilic contaminants
Facilitated diffusion –carrier molecule
Active transport (against gradient, need energy) –ion pumps
Endocytosis (need energy)

Uptake either: passive (no energy), active (needs energy, ATP)

Question 5

Biotransformation can enhance: (4)

Answer 5

Elimination: if lipophilic contaminant becomes more hydrophilic (more easily excreted in urine)
Detoxification: if contaminant made less toxic
Sequestration: to form stored away from sites of action
Toxicity: can be made more toxic, activation

Question 6

Binding and sequestration by metallothionein

Answer 6

Small pr w lots of cysteine, capable of binding several metal atoms
Found in many vertebrates and invertebrates, some plants
Produced after metal exposure, (bind to metals=) reduce metal toxicity
Plants also produce phytochelatins

Question 7

Biomineralization

Answer 7

some (lead) sequestered and eliminated this way, incorporated into shells, exoskeletons, bone, also found in granules in gut of invertebrates

Question 8

Outbreak of radium poisoning in 1925

Biomineralization example

Answer 8

Young women in watch factory –exposed to radium paint (glows in dark)
Told paint was harmless
Lick the paint brush to get a fine line while painting, used in cosmetics (lipstick)
Built up of radium in bones –suffered pain in their bones, teeth fell out, bone cancers, necrosis

Question 9

Phase I enzymes

Organic contaminants biotransformation

Answer 9

add reactive groups (OH, NH2, etc.), increase reactivity and hydrophilicity, mainly thru oxidation rxns, can be eliminated or further transformed by phase II enzymes

Question 10

Phase II enzymes

Organic contaminants biotransformation

Answer 10

add conjugates (cysteine, sulfate, glycine, glutathione, etc.), inactivates molecule and makes it more hydrophilic

Question 11

Phase I enzymes: cytochrome P-450s

Answer 11

Contaminant can become nontoxic or more toxic
P450 gene responds to contaminants by producing enzymes, induced by exposure to many types of chemicals including PAHs, dioxins, PCBs
Enzymes introduce functional group onto molecule
Used as biomarker for exposure

Question 12

Storage sites in body (4)

Answer 12

Liver and kidney: concentrate more contaminants than all other organs combined Adipose tissue: lipophilic chemicals accumulate here
Bones: chromium, lead, cadmium, radium, strontium accumulate in bones
Nails, hair

Question 13

Elimination mechanisms (4)

Answer 13

Glutathione S-conjugate export pump: phase II compounds with glutathione conjugates are removed

Organic anion transporters: neg charged organics removed, also mercury bound to cysteine

P-gp pump: In membranes, first line of defence for some contaminants
- actively pumps them back out, flipped out before toxicity can occur

Na/K ATPase: can move metals out of cells

Question 14

Main routes of elimination for plants

Answer 14

transformation, leaf fall, herbivore grazing, evaporation from surfaces, exudation from roots

Question 15

Main routes of elimination for animals

Answer 15

transport across gills, exhalation from lungs, bile secretion, secretion from hepatopancreas/intestinal mucosa (not humans), shedding of granules (insects), feces

Question 16

Gills (fish)

Answer 16

Less lipophilic compounds –excreted rapidly

More lipophilic compounds –more slowly

Question 17

Lungs (mammals, birds)

Answer 17

Chemical with low solubility in blood –fast excretion (higher vapour pressure)
Chemical with high solubility in blood –slow excretion
Particulate matter –by ciliary escalator or microphages

Question 18

Bile (from liver to feces)

Answer 18

large, more lipophilic molecules, also metals and metalloids complexed with proteins

Question 19

Kidneys (into urine)

Answer 19

more important for smaller organic molecules and metals

Question 20

Other routes of elimination

Answer 20

Sweat and saliva
Hair/fur/feathers/scales/skin
Milk and fetus (mammals) – for lipophilic substances, some metals
Eggs (birds, fish, reptiles, amphibians) –for lipophilic compounds