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?

Activation

Activation

metabolismActivation

Excretion pesticides plants

excretion

o Limited excreation via roots and via volatilization

o Deposition:Glycosides mainly in the vacuoleAmino acid conjugates mainly in the cell wall

o Possibility for deciduous species to remove xenobiotics