Pesticide Toxicology Week 2: - PowerPoint Presentation

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Pesticide Toxicology

Week 2:

Organophosphate

Insecticides

a. Acute toxicity

Categories of Effects

Muscarinic

Mimic action of muscarine

Peripheral nervous system onlySmooth muscle, heart, exocrine glandsBronchoconstriction, salivation, lacrimation, perspirationNausea, vomiting, diarrhea, crampsUrination, defecationBradycardia, miosisNicotinicMimic action of nicotineNeuromuscular junction of voluntary musclesMuscle weakness (including respiratory muscles)Twitching, cramps, pallorElevated blood pressure, tachycardiaCNS symptomsConfusion, restlessness, irritability, slurred speech, Insomnia, emotional instabilityComa

Time Course of Toxicity

Onset of symptoms

Minutes

Sarin, parathion, TEPPHoursEPNDaysChlorpyrifosAbatement of symptomsSlow onset tends to mean slow abatementAcute symptoms rarely last more than a few daysRegeneration of AChE takes ~ 1 monthAmple opportunity for re-intoxication

Chronic Effects of OPs: OPIDN

Organophosphate-induced delayed neuropathy (neurotoxicity)

Caused by subset of AChE-inhibiting OPs but not due to AChE inhibition

Delayed onsetSymptoms begin 7-30 days after exposureRecovery continues up to 1 yearPermanent effectsLongest axons most vulnerableMechanismInhibition of neurotoxic esteraseAxonal damageDeath of neuron

OPIDN:

O

rgano

phosphorus ester-induced delayed neuropathyDying back axonopathyIt is not due to inhibition of AChE (acetylcholinesterase)Only compounds that can inhibit AChE cause it.So it is presumably an esteraseMay result from single exposure Or from multiple smaller exposuresIrreversibleRats and mice do not become paralyzedAdult hens become paralyzedChicks do not.Human children do become paralyzedAn estimated 100,000 people worldwide have been affected

Leptophos (Phosvel™)

Leptophos: How Not to Identify a Neurotoxicant

Case history on website deals more with the regulatory process than with toxicology.

Chronic Effects of OPs: Reproductive Toxicity

Avian

Subset of OPs

Inhibition of AChEInhibition of kynurenine formamidaseMammalianNo physical defects due to AChE inhibitionHuman evidence for developmental CNS damageChlorpyrifos (Dursban)Delayed neuropathy also causes erectile dysfunction

Chronic Effects of OPs: Miscellaneous

Intermediate syndrome

Subset of insecticidal OPs

Onset delayed for several daysNot OPIDNRecovery?Long-term CNS effectsEpidemiological evidenceDocumented by EEG after sarin exposureGulf War syndrome?

Regulatory Aspects of OP Toxicity

What is the measure of toxicity

Symptoms

AChE inhibitionChE inhibition

Ecotoxicology

Chemical attributes

Persistence

Potential for bioaccumulationEcosystem effectsSecondary poisoningTemporary changes in ecosystemPermanent changes in ecosystemEcosystem simplificationStressed ecosystemsReproductive toxicologyNon-mammalian speciesEvolutionary consequences of efforts at extermination

Bioaccumulation and Persistence

OPs are

More water soluble than OCs

Less persistentDays or months, not yearsMalathion (outdoors)Bioaccumulation is unlikely

Secondary poisoning

May result from

Rapid lethality + residue

Fenthion used as avicideLD50 5 mg/kg in birds250 mg/kg in ratsWeakened targetCooper’s hawk in S AmericaHard to detectSmall dead organisms disappear fast

Temporary changes in ecosystem composition

Insecticides kill insects

Disrupts food supply for

InsectsFishMammalsBirdsAgricultural applications occur during springprimary breeding seasonSingle applications should be repairable

Reproductive toxicity

Difficult to assay

Stage-specific

Species-specificHistorical ExamplesOrganochlorinesDDT thins birds’ eggshellsPCBs cause malformationsDioxin-like chemicals cause GLEMEDS in troutOPsMalformations in birdsSprayed on quail eggsSite specific, not globalLocal effects repairable if no other stresses occur

Ecosystem Simplification

Elimination of already stressed species

Destruction of habitat

HerbicidesLarge-scale agricultureMonoculturesLack of hedgerows

Consequences of evolutionary pressures

Resistance

Degradation of chemical

Insensitivity to chemicalBlocking entry of chemicalOtherWestern corn rootwormDieldrinMigration rate?Crop rotationOverwintering cycleEgg laying behaviorMalaria control and mosquito behavior