PesticidesPoliclorurati

Sulfur powder used as pesticideEgypt, 1000 BC

Strychnine in 1600 ADagainst rats

Epidemic typhus (also called "camp fever", "jail fever", "hospital fever", "ship fever", "famine fever", "putrid fever", "petechial fever", "Epidemic louse-borne typhus,"[1] and "louse-borne typhus"[2]) is a form of typhus so named because the disease often causes epidemics following

wars and natural disasters. The causative organism is Rickettsia prowazekii, transmitted by the human body louse (Pediculus humanus corporis). Feeding on a human who carries the bacillus infects the louse. R. prowazekii grows in the louse's gut and is excreted in its feces.

The disease is then transmitted to an uninfected human who scratches the louse bite (which itches) and rubs the feces into the wound. The incubation period is one to two weeks. R. prowazekii can remain viable and virulent in the dried louse feces for many days. Typhus will

eventually kill the louse, though the disease will remain viable for many weeks in the dead louse.

Napoli, WW2

ESPOSIZIONE

River blindness

Black flycarrier of

eggs:Onchocerca

volvulus(nematode)

Sito di azione dei pesticidi:

• Trasmissione assonale (organoclorurati)

• sinapsi (organofosforici)

DDT

Paul Hermann Muller, Nobel prize

Aldrin

Mirex

Lindane

Characteristiche

• bassa volatilità

• molecole cicliche e lipofile (no dilavamento)

• chimicamente stabilissime (cloro non si stacca !)

• ... e quindi difficili da metabolizzare !

Metabolism is soooo...slow!!

Risultato:

• persists in environment and organisms !!

• accumulates in food chain

Bio-accumulation

DDT blocks IN AN OPEN POSITIONthe voltage-gated sodium channel

and IN A CLOSED POSITIONpotassium channels

in PERIPHERAL NERVES=>persistent DEPOLARIZATION

Na+ channel

DDT blocks the voltage-gated sodium channel

The toplogy diagram above shows the locations of mutations conferring resistance to DDT and similar drugs. Each one represents mutants identified in resistant houseflies, fruit flies, mosquitos, or moths. The important mutations are substitutions at the 932 position normally occupied by leucine (L932) and at the 929 position normally occupied by threonine (T929) (blue dots). For example, the substition of

isoleucine for threonine at 929 (T929I) confers almost complete resistance to DDT.

Incidently, the methionine at 918 (M918) is what confers sensitivity to DDT in the insect voltage-gated Na+ channel. Other animlas have a different amino acid at this position and they are not sensitive to

DDT.

Aldrin, Mirex, Lindane block sodium-potassium ATPase... and chloride channel GABA receptors (CLOSED

POSITION!)IN CNS !!

OUT

IN

Other effects:

• Induction of liver metabolic enzymes...

• accelerates metabolism of other drugs...

• like, e.g., birth-control estrogens...

• Result: