Insecticides 2

Question 1

BHC general info– structure and uses

Answer 1

benzene hexachloride (aka hexochlorocyclohexane, HCH); present in 5 isomers, with the gamma isomers displaying insecticidal activity (known as Lindane); used as a household fumigant, a seed dressing (being phased out in SK), and still used to treat lice in humans and animals

Question 2

cyclodienes general info

Answer 2

used as soil insecticides (e.g. termites); cancelled in NA in 1970s; endosulfan is a molecule in this category; highly persistent;

Question 3

acute toxicity of cyclodienes?

Answer 3

GABA inhibior; bioaccumulates and acts as an endocrine disruptor

Question 4

polychloroterpenes general info

Answer 4

toxaphene the most used derivative; persistent, but metabolized more easily than cyclodienes (less toxicity to non-target species); also a GABA inhibitor

Question 5

mechanism of toxicity for gamma HCH, cyclodienes, and polychloroterpenes

Answer 5

inhibits action of gamma-amino-butryric acid–>inhibitory NT; GABA acts to increase cell permeability to Cl, which hyperpols the cell–> makes it harder to induce an AP, cell decreases in excitability; these insecticides inhibit GABA–>leads to excitability;
also may inhibit Ca/Mg ATPase

Question 6

OP general info–derivative, properties, effects

Answer 6

organophosphates; esters of phosphoric acid; extremely diverse in physical, chemical, and toxicological properties; include broad-spectrum insecticides; have acute toxic effects on the CNS via cholinesterase inhibitions; still used

Question 7

OPs compared to OCs?

Answer 7

OPs much more acutely toxic, but less persistent than organochlorines

Question 8

carbamates–derivative, properties, effects

Answer 8

esters of carbamic acid; include broad-spec insecticides; has acute CNS toxicity via cholinesterase inhibition; typically less persistent/toxic with lower mammals, compared to OPS; however it is water sol which is bad for fish; of wide use in all sector;

Question 9

examples of carbamates used?

Answer 9

carbaryl–first successful carbamate;

carbofuran–versatile, but highly toxic to birds–>applied as pellets, birds thought it was food

Question 10

OP/carbamate mech of toxicity?

Answer 10

phosphate or carbamate binds to serine in ACE, causes blockage of the enzyme; over time, water can further cement this reaction and almost make it irreversible

Question 11

treatment of OP poisoning?

Answer 11

Atropine, 2-PAM, benzodiezapines

Question 12

what is the function of atropine?

Answer 12

muscarinic receptor antagonist, blocks parasym effects (must be used with extreme caution)

Question 13

what is the function of pralidozome (2-PAM)?

Answer 13

reactivates ACE–> binds to OP, changes conformation, makes it want to leave ACE

Question 14

what is the function of benzodiezapene?

Answer 14

reverses the anxiety of CNS (GABA enhancer)

Question 15

what is chronic OP toxicity?

Answer 15

neurophysiological and behavioural effects (changes in memory, academic skills, motor skills, “abstract thinking”); neuropathological effects– “OP-induced delayed neuropathy (OPIDN)–> characterized by mainly leg and arm weakness;

Question 16

what does chronic OP toxicity mainly arise from?

Answer 16

occupational (high) exposures (ag workers, pesticide manufacturing, “sheep dipper’s flu”, chronic fatigue, gulf war syndrome);

Question 17

hypotheses underlying the mech of action of chronic OP toxicity?

Answer 17

1. neuropathy target esterase (NTE) thought critical in the initiation of OPIDN
2. Desensitization (downregulation) of cholinergic receptors in CNS and PNS
3. altered nicotinic and/or muscarinic autoreceptor function (on presyn nerve)
4. alterations to high affinity choline uptake transporters

Question 18

major concerns of OP toxicity?

Answer 18

long term, subtle effects on infants and children; IQ scores decrease with exposure, issues in gait; young individuals appear to be more sensitive to effects (acute and chronic) of AChE inhibitors–
young have reduced paraxonase-1 or SNPs = altered enzyme efficacy