ECOTOX TOXICODYNAMICS

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 

1. target molecule (3 main types)

2. interaction type at target site (3 main types)

3. type of effect

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) 

- 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 

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) 

-> 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 

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) 

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