Pesticide Application, transport and effects Lars Schrübbers Jens C. Streibig Il Buono, il Brutto, il Cattivo Jens C. Streibig Plants The flowering plants • Good Wild and cultivated plants • Bad Weeds • Ugly Noxious weeds
Pesticide Application, transport and effects
Lars Schrübbers Jens C. Streibig
Il Buono, il Brutto, il Cattivo
Jens C. Streibig
Plants
The flowering plants
• Good Wild and cultivated plants• Bad Weeds• Ugly Noxious weeds
Outline • How compounds enter an organism
• How is the compound are distributed in the organism
• What happens with the compound within the organism
• How (if) does the compounds leaves the organism
A – AbsorptionD – DistributionM – MetabolismE – Elimination
+ toxicity
Uptake
• Plant cuticle• Animal skin• Animal cuticle (insects)• Inhalation• Digestive tract
• No uptake
uptake
uptake
Cuticle
Devine et al 1993
hydrophobicity
uptake
hydrophilicity
Uptake?
uptake
Cuticle and skin
uptake
important: vehicle (donor liquid), molecular size, skin properties (injury etc.) ...
e.g.: very polar compound in water, or an organic solvent as carrier.
Ngo 2009
name Log P o/w permeability coefficient (μm/h)
glyphosate -1.7 0.04
caffeine 0.16 4.5
benzoic acid 1.83 51
malathion 2.75 4.45
important: vehicle (donor liquid), molecular size, skin properties (injury etc.) ...
Terrestrial animals
• Skin• Lungs (inhale)
– Specialized to selective molecular uptake• Gastrointestinal tract (swallow)
– Specialized to selective molecular uptake
uptake
uptake
Eventually herbicides must enter living cells to cause the desired effect
e.g.:Photosynthesis –ChloroplastRespiratory –MitochondriaALS – Chloroplast...
distribution
Phloem:2,4-DGlyphosateImazapyrHaloxyfop
Xylem:AtrazineBenomylThiophanate methylDimethoate
Distribution
Uptake and Translocation
distribution Chemical properties and mobility
Devine et al. 1993
distribution
Penetrating membrane:
- Non-polar- MW lower than 1000 g/mol- Actively transported
distribution
Ion trapping
Gastric juice, pH = 1.4 Plasma, pH = 7.4
Opposite for weak bases!
Seven routes to death1. Enzyme inhibitors2. Disturbance of signal systems3. ROS (Reactive Oxygen Species)4. Degrading pH gradients (proton pumps)5. Dissolving membranes6. Disturbing osmotic balance or pH7. Strong electrophilic compounds
J. Stenersen 2004
toxicity
Toxicity
Oral (LD50) Dermal (LD50) Class Property
Solid Liquid Solid Liquid Ia Extremely hazardous _5 <20 <10 <40 Ib Highly hazardous 5–50 20–200 10–100 400–400 II Moderately hazardous 50–500 200–2000 100–1000 400–4000 III Slightly hazardous >500 >2000 >1000 >4000 Active ingredients unlikely to present acute hazard
Classified using animal LD50s (oral: rat, dermal: rat or rabbit)
The relative toxicity of compounds in human poisoning is complicated by theease of treatment — for example, class I organophosphorus pesticides can be treated with atropine and oximes with some effect, whereas selfpoisoningwith class II organochlorines is practically untreatable in many locations
WHO Hazard Classes
toxicity toxicity
The Globally Harmonized System of Classification and Labeling of Chemicals” (GHS)
Examples toxicity
Aluminium phosphide is used as a rodenticide, insecticide, and fumigant for stored cereal grains. It is used to kill small verminous mammals.
The acid in the digestive system of the rodent reacts with the phosphide to generate the toxic phosphine gas.
In 2002, Sir Derek Bibby, (Bibby Line shipping company) aged 80 and terminally ill with leukaemia, committed suicide by the use of aluminium phosphide
- the poison, hours later, caused his body to emit dangerous fumes forcing the evacuation of the hospital department where his body was being held
AlP + 3 H2O → Al(OH)3 + PH3
AlP + 3 H+ → Al3+ + PH3
toxicity
At the site of action I50-Levels for an ALS inhibitor
Four routes to recovery
• Conversion• Conjugation• Deposition• Excretion
metabolism
Metabolism
metabolism
Not to confuse withsecondary metabolite
Even though same enzymes might be used…
metabolism
mammals plants
mobility mobile immobile
carbon source heterotroph autotroph
circulatory system well developed poorly developed
special organc for toxification liver -excreation of water solulable metabolites yes limited
CYP 450 + +glutathion conjugates + +Amino acid conjugates + +
sulphate conjugates + -glucuronic acid conjugates + -glucose conjugates - +phase III metabolism not important important
Comparative metabolism
Comparative animal/plantmetabolism
Glutathione:
Gamma-Glutamyl-cysteinyl-glycine,GSH, tripeptide
metabolism
Metabolism
Devine et al 1993
metabolism
Diflubenzuron
Deactivation
metabolism
Deactivation
metabolism
metabolism
Conjugation reaction (phase II metabolism)
metabolism
...mercapturic acid/malonic acid pathway
metabolism
ether glucuronideDDT
?
methoxychlor phenolmethoxychlor
Example for phase II metabolism:
+ UTP
- P2O74-
+ 2 NAD+
- 2 NADH+
UDP-glucuronic acid
O
OH OOH
OH
CH2OH
P
OH
O
OH
glucose-1-phosphate
+
HC
Cl ClCl
OO
OH
O
OH
OH
COOHCH3
+ UDP
Glucuronosyl
transferase
HC
Cl ClCl
OO
OH
O
OH
OH
COOHCH3
Glucuronide
Glucoside
mammals
plants(and insects)
Mammal or plant?