ECOTOX TOXICOKINETICS PART 1 & 2
VL3, VL4
VL3, VL4
Set of flashcards Details
| Flashcards | 16 |
|---|---|
| Language | Français |
| Category | Biology |
| Level | University |
| Created / Updated | 18.05.2023 / 21.05.2023 |
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Basic remarks for toxicokinetics on the organism level (4)
1. uptake > elimination -> bioaccumulation
2. the concentration of a chemical in the tissue of an organism is time & mass/size dependent
3. the elimination rate of a chemical is time & concentration dependent
4. pseudo elimination = growth dilution (persistent chemical taken up at young age -> concentration decreases with increasing growth)
How do you determine tissue concentrations & BCF (in the lab) (2 phases)
1. Phase: the exposure to the contaminant at a constant concentration -> uptake & elimination
-> wait until concentration in tissues is at SS -> calculate BCF = ctissue/cwater = ku,w/ke (BMF = ctissue/cdiet = ku,d/ke)
BUT: reaching SS can take a long time, can be more efficient to determine BCF based on uptake & elimination rates
2. Phase: depuration, contaminant is removed -> only elimination happens
Biomagnification Factor BMF & Interpretation (3)
= a measure of the increase of a chemical in organisms across trophic levels: czooplankton/cphytoplankton
BMF <1: chemical is effectively metabolized/eliminated by the organism
BMF >1: chemical accumulates from the diet in zooplankton
Example: bioaccumulation kinetics of PCB's in Rainbow Trout
- background (2)
- what concentrations do we expect in fish at SS? (2)
- How long will it take (after exposure) to eliminate 50% of the chemical? (t1/2) (1)
- researchers have found elevated PCB levels within crabs
- PCBs = endocrine disruptors
-> BCF = Corg/Cw = ku,w/ke at SS -> Corg (SS) = Cw * ku,w/ke (if you increase Cw by 2, Corg increases by 2 but BCF stays the same, as ratio)
- we have an allometric relationship for the bioaccumulation in fish; uptake rate depends on size for chemicals with logKOW >3
- t1/2 = ln(0.5)/-ke -> elimination is also heavily size/weight-dependent
Summary; both chemical (3) and biological (6) traits determine the final concentration
chemical: solubility, molecular size, partitioning behavior, degree of chlorination/halogenation (examples)
biological: organism composition (protein, lipids); feeding routes (water, sediments), diet, physiology, growth rate, feeding behavior (feeding rate), assimilation efficiency, temperature, size of organism
Define Toxicokinetics
= what a cell/organism can do to a chemical
Explain the role of the cell in toxicokinetics (4)
1. fundamental unit for providing all toxicokinetic processes
2. cell wall + membrane as important barriers for toxins
3. cell membrane & surface proteins/channels are key for uptake & elimination of chemicals/toxins
4. cellular compartments are important: depending on their composition (protein like nucleus, lipid like membrane), depends where chemical will end up
Name the 4 most important toxicokinetic processes
1. passive transport (incl. facilitated transport)
2. active transport
3. endo,- & exocytosis
4. biotransformation
Active transporters: name the 2 implications for ABC transporters
function as:
1. active "internal barriers" -> blood/tissue, liver, kidney -> multidrug resistance
2. active "environment-tissue barriers" -> external surfaces like gills/lungs, intestine -> multixenobiotic resistance
Name reactions (3) & main enzyme as well as main goal of phae I biotransformation
1. oxidation (loss of electrons), 2. reduction (=gain of electrons),3. hydrolysis (addition of water)
Enzyme: Cytochrome P450
goal: increase the chemical in polarity and size -> make it more hydrophilic
Name the 3 main (intended) reactions during Phase II biotransformation
1. glucuronide conjugation (via UGT)
2. sulfate conjugation (via SULT)
3. glutathione conjugation (via GST)
Explain how Phase I and II biotransformation eznymes are regulated:
(2)
1. via constant expression: generally kept at low level
2. inducible expression: upregulation of the enzyme upon need/when conditions/cellular environment change
Name & Explain an example for induction of biotransformation enzymes (6)
Receptor-mediated activation via AHR
1. chemical enters cell & binds receptor
2. receptor-complex undergoes conformational change
3. transport to nucleus
4. binding to DNA responsive element
5. DNA transcription is activated
6. Phase I&II enzymes or ABC transporters expression/activation induced
Can you explain the role of biotransformation products in the environment?
(2)
1. biotransformation products can be eliminated or also pose an environment risk: one parent molecule can give rise to many transformation products, which are usually less, but sometimes more toxic
2. biotransformation products are generally more stable and more mobile (which makes them more prone to leach into groundwater)
How do biotransformation products become more toxic? (3)
1. the active moiety remains intact during biotransformation
2. if the uptake is enhanced due to pH-dependence of increased hydrophobicity (Kow)
3. if the transformation results in a product with a different & more potent mode of action
Name 3 examples where biotransformation results in more toxicity
1. allyl alcohol in adult zebrafish is more toxic as in embryos as they are better at biotransformation & produce more acrolein, which is toxic
2. cocaine is turned into a liver toxicant when present with phenoarbitrol as phenoarbitrol induces CYP which biotransforms cocaine to a liver toxicant
3. the (already biotransformed) epoxide of aflatoxin is sterically difficult to reach for biotransformation enzymes and thus a spontaneous reaction with DNA (covalent binding) and adduct formation can happen faster
