Pesticides Flashcards
Organochlorine insecticides (caged structures) NAMES
mirex
chlordecone (Kepone)
Organophosphorous insecticides
chlorpyrifos (Dursban, Lorsban), acephate, malathion, dichlorvos
toxicity occurs at the synapse
inhibition of AChE
SLUGEM/SLUG/SLUD
atropine -> ACh receptor antagonist
2-PAM -> regenerates AChE
Type II pyrethroids
CS sydrome
Salivation, tremors progress to choreoathetosis, clonic seizures
prolong Na channel openings longer -> depolarization block
Captan and folpet
broad-spectrum protectant fungicides; together with captafol, they are called chloroalkylthio fungicides,
potent eye irritants, but only mild skin irritants.
induce the development of duodenal tumors in mice,
Klaassen, Curtis D.; Watkins, John B.. Casarett & Doull’s Essentials of Toxicology, Third Edition (Lange) . McGraw-Hill Education. Kindle Edition.
Organophosphorous insecticides
NAMES
chlorpyrifos (Dursban, Lorsban)
acephate
malathion
dichlorvos
Organochlorine insecticides (Chlorinated ethane derivatives) NAMES
DDT
methoxychlor
Organochlorine insecticides (caged structures)
mirex, chlordecone (Kepone)
tremors (not seizures); hepatosplenomegaly; repro tox
Kepone (kepone shakes)
Green tobacco sickness
dermal absorption of nicotine from leaves
Activates nAChR -> nausea, vomiting, muscle weakness, rapid heart rate
Rotenone (rotenoids)
from roots of tropical leguminous plants in Asia and C and S America
Animal model for Parkinson’s (selective nigrostriatal degeneration)
inhibits mitochondrial respiratory chain (Complex 1) - by blocking electron transport at NADH–ubiquinone reductase
Klaassen, Curtis D.; Watkins, John B.. Casarett & Doull’s Essentials of Toxicology, Third Edition (Lange) . McGraw-Hill Education. Kindle Edition.
α-naphthylthiourea (ANTU)
lethal yet tasteless to rodents, while being of low toxicity to humans
main target of toxicity is the lung, where ANTU causes marked edema of the subepithelial spaces of the alveolar walls mediated by an inflammatory response.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 1093). McGraw-Hill Education. Kindle Edition.
Type I pyrethroids
T syndrome (tremors)
arousal, aggression, exaggerated sensitivity to stimuli
prolong Na channel openings -> repetitive firing
dithiocarbamates
fungicide
most are associated with metal moieties
chronic exposure is associated with adverse effects metabolized to a common metabolite, ethylenethiourea, that is responsible for the effects of dithiocarbamates on the thyroid, which include hypertrophy and hyperplasia of thyroid follicular cells that progress to adenomas and carcinomas.
nomenclature of many of these compounds arises from the metal cations with which they are associated; thus, there are maneb (Mn), ziram and zineb (Zn), mancozeb (Mn and Zn), and ferbam (Fe). Thiram is an example of dithiocarbamate without a metal moiety
resembles that of disulfiram, a compound used therapeutically to produce intolerance to alcohol,
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 1090). McGraw-Hill Education. Kindle Edition.
Klaassen, Curtis D.; Watkins, John B.. Casarett & Doull’s Essentials of Toxicology, Third Edition (Lange) . McGraw-Hill Education. Kindle Edition.
Organochlorine insecticides (Chlorinated ethane derivatives)
DDT, methoxychlor
sodium channel activators
poorly absorbed through skin
acute oral tox -> tremors, convulsions, seizures, hyperactivity, hyper-susceptibility to stimuli; death due to respiratory failure
chronic tox -> hepatocellular hypertrophy, CYP induction, liver cancer (rat); stored in adipose tissue; endocrine active; possible association with testicular cancer
estrogenic effects
Pyrethroids
synthetic pyrethrins
very potent and not stable in environment
low mammalian tox
poisoning manifests as hypersensivity, tremor, seizures
activate voltage gated sodium channels (Types 1 and 2)
Type II pyrethroids also bind to and inhibit GABAa-gated chloride channels
do not require bioactivation
Carbamate Ester Insecticides
NAMES
aldicarb (Temik)
carbaryl (Sevin)
Chlorphenoxys
systemic herbicide (2,4-D; 2,4,5-T)
acute tox -> vomiting, burning of mouth, abdominal pain, hypotension, myotonia, CNS effects, coma
dioxin contamination - Linked to soft tissue sarcomas and lymphomas; Parkinson’s; cancer in pets
Tx: bicarbonate to alkalinize urine, which reduces nonionized fraction and decreases reabsorption
Mx: cell membrane damage, interference with metabolism involving acetyl CoA, uncoupling of oxidative phosphorylation
dinitroorthocresol
DNOC
uncouples cellular oxidative phosphorylation
fever
Carbamate Ester Insecticides
Aldicarb (Temik) and carbaryl (Sevin)
don’t require metabolic activation
acute intoxication similar to OPs, but resolve in hours
Tx: atropine, no 2-PAM
transient and reversible interaction with AChE
Sodium fluoroacetate (compound 1080)
control mammalian pests
similar to acetate -> combines with CoA to form fluoracetyl CoA which can substitute for acetyl CoA and reacts with citrate synthase to produce fluorocitrate -> a metabolite binds tightly to aconitase, halting the TCA cycle
Red Squill
affect the cardiovascular and central nervous systems and cause emesis; the inability of rodents to vomit explains the rather selective action in these species
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 1093). McGraw-Hill Education. Kindle Edition.
Neonicotinoid insecticides
nicotine and other nAChR agonists
exploit differences btwn insect and human nAChR
Organochlorine insecticides (cyclodienes) NAMES
chlordane heptachlor aldrin dieldrin toxaphene
Organochlorine insecticides (cyclodienes)
chlordane, heptachlor, aldrin, dieldrin, toxaphene
inhibit chloride channels
high acute mammalian tox
well absorbed through skin
seizures; no tremors
Thallium Sulfate
Because of its very high acute toxicity (LD50 in humans = 8–15 mg/kg), the use of thallium sulfate as a rodenticide has been banned in the United States in 1972,
Thallium is a mitochondrial poison and has a high affinity for sulfhydryl groups. Main effects of thallium poisoning are peripheral neuropathy, toxic encephalopathy, and alopecia
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 1093). McGraw-Hill Education. Kindle Edition.
Bipyridyl derivatives
paraquat and diquat
paraquat is lung toxicant regardless of route of exposure
accumulates in type I and II epithelial cells and club cells
Mx: production of superoxide anion and hydroxyl radicals -> lipid peroxidation and cell death; depletion of NADPH; mitochondrial damage
Organochlorine insecticides (hexachlorocyclohexanes)
lindane
seizures, liver and kidney damage, skin sensitization
neutropenia
readily absorbed through skin
Diamides
ryanodine (Ca channel receptor) agonists
-> activate ryanodine receptors in insect muscle -> depletion of calcium -> paralysis and death
2,4-D
2,4-D is not Agent Orange. Agent Orange was a mixture of two different herbicides: 2,4,5-T and 2,4-D (as well as kerosene and diesel fuel). 2,4,5-T contained high levels of dioxin
can be safely used
broad-leaved plants
elemental sulfur
dermatitis
