ECOTOX TOXICODYNAMICS
VL6 & VL7
VL6 & VL7
Kartei Details
| Karten | 12 |
|---|---|
| Sprache | Deutsch |
| Kategorie | Chemie |
| Stufe | Universität |
| Erstellt / Aktualisiert | 19.05.2023 / 31.05.2023 |
| Weblink |
https://card2brain.ch/box/20230519_ecotox_toxicodynamics
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| Einbinden |
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Explain the interplay between primary & secondary effects
cells = central site of chemical-organism interaction
if the chemical manages to enter the cell (despite phase 0 cellular defense) a primary interaction can take place -> leads to primary effects (enzyme inhibition, covalent binding) -> if not repaired: secondary effects (skin lesions, reduced growth)
primary interaction can also lead to phase I & II biotransformation which then either leads to 1) detoxification & export, or 2) bioactivation & a more toxic transformation product
What does a primary interaction in a cell consist of (3)
1. target molecule (3 main types)
2. interaction type at target site (3 main types)
3. type of effect
Name the 3 basic types of target molecules and their type of interaction
1. membranes (lipids) -> cell membranes, organelles -> non-specific
2. peptides & proteins -> enzymes (catalytic function), transporters (ABC, ion channels), regulation (transcription factors), structural proteins -> specific
3. DNA -> reactive (formation of covalent bonds, biotransformation)
What is baseline toxicity (3)
- lowest intrinsic "minimal" toxicity: change of membrane fluidity/disturbance of channels -> all substances display baseline toxicity, as they have to enter through the membrane
- reversible
- also called narcosis
Whats a QSAR for baseline toxicity
QSAR = quantitative structure activity relationship -> correlation between toxicity of a chemical and it's structure -> you can predict the LC50 (toxicity) of a chemical based on it's KOW (use DOW for ionized substances)
for polar narcosis: use membrane-water partition coefficient (Kmw) instead of KOW, as KOW cannot predict polar narcosis well. (Distinction between polar & non polar is only made when KOW is used)
What is the toxic ratio, why do we need it
-> measured toxicity values can differ from predicted ones (due to eg different amounts of fat tissue, or rate of biotransformation)
the TR compared predicted & experimental LC50 (predicted/experimental) and indicates wether a chemical exhibits higher than just baseline toxicity
1. baseline toxicants are expected to have a TR of about 1, and their measured LC50 should lie close to the QSAR line
2. a measured LC50 below the QSAR line indicates a specific/reactive mode of action (measured will be smaller than predicted; ie more toxic)
TR 1 -> baseline (non-polar narcosis)
TR 5-10 -> baseline (polar narcosis)
TR 10-10^4 -> reactive/specific mode of action
Would you expect a specific effect of the following chemicals in short-term toxicity tests in either fish, daphnia or algae?
- Benzene
- Sodium Dodecyl Sulfate
- Terbutryn (Herbicide)
- Cypermethrin (Insecticide)
- BPA (endocrine disruptor)
Benzene -> apolar -> baseline toxicant -> NO
SDS -> apolar tail, polar head -> like phospholipid -> baseline toxicant -> NO
Terbutryn: Herbicide -> Fish & Daphnia NO, algae YES
Cyperrmethrin: Insecticide -> Fish & Daphnia YES, algae NO
BPA -> NO for short-term tests, YES for long-term tests (in all 3 species)
Explain the concept of lethal (critical) body burden
(2)
1. ILC50 = internal lethal concentration that causes 50% mortality = LC50 x BCF
2. Estimate: for death due to baseline toxicity (acute lethality), the CBR is generally between 2 and 8 mmol/kg wet weight
Pratical applications & consequences for LBB
(3)
1. the level of the CBR has been shown to be similar for different species -> can extrapolate to other species
2. the lvel of CBR is independent of exposure scenarios or time -> facilitates comparison between different toxicity tests and exposure scenarios
3. the CBR helps to link exposure and effect modelling
Specific Mode of Action affecting Membranes: Name 4, explain shortly and name an example for each
1. inhibition of ETC via redox cycling -> chemical that can capture electrons (electron acceptor) can transfer them to oxygen and form radicals -> chemical goes back to normal and can start over again (eg Quinones)
Example: Paraquat
2. Competitive binding to electron transport proteins
Example: Competitive binding of Diuron to QB domain of pheophytin (= first electron carrier in ETC of photosystem II in plants) inhibits photosynthesis
3. Uncoupling & Disruption of Proton Gradients
- The chemical is negatively charged and gets protonated in intermembrane space -> in matrix it releases proton -> destroys proton gradient built up by ETC
Eg Dinoseb -> dissociates at pH 7 in the matrix.
4. Enzyme inhibition -> ATP Synthase
- chemicals can bind to inhibitory site of ATP Synthase
Example: Organotin
Specific Mode of Action Affecting Peptides/Proteins: Name 3, explain briefly and name an example for each
1. Enzyme inhibition
Example: Triclosan -> inhibits enzyme in fatty acid synthesis; Diclofenac: inhibits COX (which converts arachidonic acid to prostaglandins) -> no more pain
2. Interference with Transmission of Nerve Pulses
interference with excitatory/inhibitory chemical synapses: sodium & chloride channels, GABA receptors, Acetylcholine receptors, acetylcholine esterase
Example: DDT: inhibits proper opening of sodium channles -> no resting potential restored -> overexcitation, tremors
Organophosphates: bind to acetylcholineesterase -> acetylcholine not degraded/much slower -> overexcitation, tremors. OP have a phospjate group and their biotransformation products are much more potent than their parent compound; eg Parathion
3. Estrogenic Compounds
Example: BPA binds to estrogen receptor & estrogen response element -> changes transctiption/translation patterns -> endocrine disruptor
Name 1 specific mode of action affecting DNA and explain with example
DNA damage & mutations
Example: Benzoapyrene: its oxidation product (epoxide) has en electrophilic center which is difficult to reach for biotransformation enzymes -> can covalently bind guanosine -> mutations if not repaired
