“The Savior of Mankind”DDT called the “Savior of Mankind” because it controlled the fleas and louse that transmitted typhus.

World War II was the first war in which casualties eclipsed deaths due to disease and pestilence.

Xenopsylla cheopsis, flea

Pediculus humanus, human body louse

…On Second Thought!!Production increased four-fold from 1945 to 1955.Widespread use in public areas and the backyards of America.1946 - 1st report of fatty tissue accumulation.1958 - Dutch elm disease and dead robins. 1962 - Rachel Carson makes fateful prediction.

The Unforeseen Effects of DDT

DDT remains effective for years. An initial selling point to farmers and the U.S. Public Health Service.Bioconcentration up the food chain.The rise of secondary pests - spider mites

Where Are We Today?Integrated Pest Management (IPM)

1. Chemicals2. Predators, Parasites

and Pathogens3. Resistant Plants4. Pheromones5. Sterilized Pests

North America is the #1 producer of foodstuffs in the world. This is largely due to our seed stock and the use of pesticides.

PesticidesA pesticide is any substance or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.

In addition, a pesticide is also any substance or mixture of substances intended for use as a plant regulator, defoliant or desiccant.

Common PesticidesAlgicides - Control AlgaeAntifouling Agents - Repel organisms like barnaclesAntimicrobials - Kill microorganismsAttractants - Attract pestsBiocides - Kill microorganismsDisinfectants and Sanitizers

FungicidesFumigants - Gas/vapor inside

HerbicidesInsecticidesMiticides - Kills Mites

Microbial Pesticides -Organisms that kill/competeMolluscicides - Kill snails/slugsNematicides - Kill nematodesOvicides - Kill insect/mite eggsPheromones - Disrupt matingRepellents - Repel insects

RodenticidesDefoliants - Cause leaf fallDesiccants - Promote dryingInsect Growth RegulatorsPlant Growth Regulators -excludes fertilizers

What is not considered a pesticide?

Drugs used to control diseases in humans or animals. (FDA)

Fertilizers and nutrients used to encourage plant survival and health.

Biological control agents. (Beneficial predators)Low risk substances such as cedar chips, garlic

and mint oil.

Pesticide LegislationThe Environmental Protection Agency oversees all pesticide programs.The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).FIFRA amended and strengthened in 1988.EPA administrator can ban any substance.

ALL pesticides registered pre-1984 must be reregistered

Animal toxicity dataTransport and fateCancer risk studiesRegister every use of pesticideNo more than six pesticides presented/yearReregistration Eligibility Decisions (RED) from EPA

Perception BiasBenlate in Nurserymen.Malathion in Hillsborough County, FLTemporality is neither an exposure

nor a dose.An exposure must be quantifiable.There must be a physiological dose.

The EPA and DursbanJUNE 8, 2000 - “To protect the health and environment of all Americans, especially children, the U.S. Environmental Protection Agency and the manufacturer of Dursban have agreed to eliminate the widely used pesticide for nearly all household purposes. Dursban, also known as chlorpyrifos, is the most widely used pesticide product in the U.S.”

EPA Administrator, Carol M. Browner

Limitations on Grapes and Tomatoes.

Potential Problems with Pesticides

Adverse environmental impact- Bioaccumulation- Persistent Soil Levels- Water Pollution- Secondary Pests - Spider Mites- Unintended loss of species

Target species resistance- Cross-Resistance to others in group- Resistance may continue after withdrawal of agent

Human Health Problems-- Acute intoxication and chronic problemsAcute intoxication and chronic problems

Labeling of Pesticide PackagesSignal Word Toxicity Acute Oral LD50

Danger High 0-50 mg/kgPoisonSkull and CrossbonesCall physician immediatelyKeep out of reach of children

Warning Moderate 50-500 mg/kgNo antidoteKeep out of reach of children

Caution Low 500-5000 mg/kgNo antidoteKeep out of reach of children

No Signal Word Relatively Safe >5000 mg/kgCriteria Established by FIFRA

Environmental and Biological Fate

Solubility and Vapor pressure- Low values = biological residual

Chemical characteristics- Volatility in sunlight

Metabolism- Organism enzymatic processes- Microorganisms

InsecticidesOrganochlorinesOrganophosphatesCarbamatesBotanicals

Organochlorine InsecticidesBroad Spectrum InsecticidesPersistent in the Environment (2-4 years)Primarily contact poisonsInexpensive

Banned in the U.S. because of bioaccumulation in the food chain due to high lipophilicity.

Categories of Organochlorines (OC)

Chlorinated ethanes- DDT, Hexachlorohexane, Methoxychlor

Cyclodienes- Aldrin, Dieldrin, Endrin, Chlordane, Heptachlor Toxaphene

Hexachlorocyclohexanes- Lindane (The only remaining OC in the US market)

Signs and Symptoms of OC Intoxication

Result in CNS stimulation - Inhibit the GABA mediated chloride channel in the CNS (Lindane)

Affects Neuronal Membranes - Na+ channels open for long periods of time (DDT), axonal changes

Neurological - fatigue, sleep disturbances, blurred vision, weakness, fainting, paresthesias, seizures, coma and death.

Gastrointestinal - Nausea, vomiting, cramping, diarrhea,increased liver enzymes, hepatomegaly, splenomegaly, proliferation of smooth endoplasmic reticulum.

Workup and Treatment of OC Exposure

Check the package for EPA warningHistory is best clue, however, levels can be

checked in serum, urine and adipose tissues.Cholestyramine for oral ingestion - activated

charcoal not shown to be helpfulControl seizures with benzos, etc.Chronic Findings - No CA association for aldrin,

dieldrin, heptachlor and chlordane

Organphosphate (OP) Insecticides

Replaced organochlorine insecticidesShort environmental lifespan (1-10 weeks)Systemic neurotoxicant to insects and

humansRapidly absorbed by all routes of

exposureRapid elimination -

low potential for bioaccumulation

OP Mechanism of ActionComplex with acetylcholinesterase enzyme in an irreversible fashion. Enzyme phosphorylation and deactivation.Accumulation of large amounts of acetylcholine.Stimulation and exhaustion of cholinergic synapses.

OP Mechanism of Action(cont.)

OP Mechanism of Action(cont.)

Organophosphorus Insecticides

Inhibition of acetylcholinesterase (AchE) results in repeated stimulation of skeletal muscles causing fasciculations and ultimate paralysis

Excessive stimulation of autonomic nervous system - excessive mucous production in the lungs

In extreme cases - death

Signs and Symptoms of OP Exposure

Assessing the Level of Exposure

Laboratory Evaluation

RBC vs. Plasma

Pseudocholinesterase

Urinary pesticide metabolites

Organophosphate Exposure

Garlic-like odor may be evidentDuration of illness depends upon severity

of poisoningMonths may be needed for cholinesterase

activity to return to normal levelsDermal exposure may cause sensitization

or irritation

Organophosphate AntidotesAtropine

- Antagonizes muscarinic and CNS symptoms - No change in muscle weakness orrespiratory failure (2-PAM)

- Reverses phosphorylation when given within 24 hours of exposure.

- An “AGED” receptor will not respond to 2-PAM.- Ameliorates muscle weakness and respiratory depression

Pralidoxime (2-PAM)

Case

The Story Continues

Resolution

Chlorpyrifos10-15 million lbs. Ag yearly, 9-12 million lbs. non-Ag usage Crop dusting, controlling fleas, cockroaches, ticks, termites, and fire antsTrade names: Dursban, Lorsban, Dursbank, Killmaster, Brodan, Eradex, Pyninex

Colorless solidSolubility - .0002% by weightVapor Pressure -.00002 mm HgActive Metabolite -Chlorpyrifos oxonHumans have a high detoxification capacity

ParathionPale yellow to dark brown with garlic odor.Vapor Pressure - .0004 mm HGSolubility - .01% by weightPotent - Lethal oral dose 10-100 mgInadequate evidence to evaluate carcinogenicity.

Methyl ParathionWhite crystalline powderVapor Pressure - .0001 mm HgSolubility - .006% by weightLethal oral dose - 2 GramsMetabolized in the liverStudies have shown a slightly higher level of chromosomal aberrations in smokers and alcoholics.

MalathionDeep brown to yellow liquid Garlic or skunk-like odor Solubility - 0.02% in water by weightVapor Pressure - .00004 mm HgUsed for Mosquito EradicationMay cause dermal sensitizationLow/moderate toxicity among the OPTrade names: ENT 17034, AC 4049, Celthion,Cythion, Formal, Karbofos, Detmol MA, Fosfothion

Carbamate Insecticides(carbaryl)

AChE inhibition similar to OP insecticidesAChE inhibition is reversibleRelatively low toxicity in humansLowest dose producing an adverse effect is closer

to a lethal dose for carbamates than for organophosphates

Trade Names: Sevin, Dragon, Green Light, Security, and Bonide

Exposure via dermal, inhalation, or ingestion

Pyrethrum(Botanical Insecticide)

Derived from chrysanthemum flowers Brown viscous oil or solidInsoluble in waterLow vapor pressureSubject to photodegradationOxidized rapidly in presence of airKnockdown insecticide

PyrethrumLow capacity for dermal absorption Low concentration in commercial productsContact dermatitis is a common reaction

associated with exposureMay lead to anaphylaxis in persons who

are sufficiently sensitizedIrritating to eyes and nasal passages

Pyrethrum:Target Organs - CNS

High affinity for open membrane sodium channels

Results in an increase in the time sodium gates are open

Leads to over stimulation of the nerve membrane

Extreme cases can result in depolarization of the nerve membrane

Pyrethrum:Signs & Symptoms

In animals, intoxication leads to excitation, convulsions, and muscle fasciculations

Chief effect in humans is dermatitis

FungicidesIn general, modern fungicides have

very low acute toxicity to humans and other mammals

Fungicides are a chemically diverse group of pesticides

Dithiocarbamates(thiram, zineb, maneb)

Structurally similar to disulfiram (Antabuse) and has a similar effect on alcohol

Carbon disulfide is a common metabolite of all dithiocarbamates

Virtually insoluble in water and most organic solvents

ThiramAbsorbed by dermal, oral, and

inhalation routes Systemic signs and symptoms:

- nausea - anorexia- vomiting - diarrhea- coma - headache- lethargy - ataxia

ThiramAlcohol has a synergistic effect on toxicity Allergic dermatitis reported in farmers Dermatitis may be aggravated by alcohol

consumptionIARC - concluded that thiram is not classified

as a human carcinogen

Captan(Phthalimide Fungicide)

White crystalline powder with a pungent odorNot a significant threat to aquatic flora and fauna

because of its low solubility and rapid biodegradation

Residues may persist on food and should be removed by rinsing

No reports of systemic poisoningNIOSH - possible occupation carcinogen ACGIH - animal carcinogen

Captan:Signs & Symptoms

If ingested may cause nausea, vomiting, and diarrhea

Dermal exposure often causes contact dermatitis

Captafol(Phthalimide Fungicide)

Persistent in soilsIARC - concluded that there is sufficient

evidence of carcinogenicity in animals and probably carcinogenic in humans

Increased liver weight and histopathological changes in animals

Captafol:Signs & Symptoms

Respiratory sensitization and occupational asthma associated with captafol

Reported to cause contact dermatitis

PentachlorophenolBenzene like odorUsed as a wood preservative and in the

textile industryPersistent in the environmentFound in surface water close to points of

application and along rights-of-wayNo report of biomagnification in food

chains

PentachlorophenolSigns and symptoms from acute poisoning

include: weakness, hyperpyrexia, metabolic acidosis, cardiac arrest, tachycardia and bronchitis

Reports of intravascular hemolysis from exposure to wood cleaners containing pentachlorophenol

Dermal exposure can cause contact dermatitis

PentachlorophenolSuspected of causing cancer and abnormalities

in the lymphoid systemNo significant damage to functional immune

responsesClusters of Hodgkin’s disease have been

associated with pentachlorophenol contaminated water and among wood workers

IARC - animal carcinogen but insufficient evidence to consider it a human carcinogen

HerbicidesSelective or non-selectiveContact or systemic actionPre or post emergence

Triazine Herbicides(atrazine, simazine, cyanazine)

May be selective or non-selective depends upon application rate

May be used as pre or post emergent Photosynthesis inhibitorsLow acute toxicityConcern that they may be carcinogenic

based on very limited evidence

ParaquatExtremely soluble in waterBinds tightly with soilActive ingredient in Criquat, Dextrone,

Dexuron, Sweep, Goldquat 276Contact herbicide

Paraquat:Target Organs

Lungs and muscle - reservoir, which slowly redistributes to the bloodstream

Ingestion leads to fibrosis of the lung tissue, samples reveal interstitial areas containing collagen, fibrin, and platelets

Toxicity is a result of a redox reaction and treatment with oxygen may enhance toxicity

If ingestion has occurred usually indicates a grim prognosis

DiquatContact herbicideIf ingested, target organ is the gastrointestinal

systemExcessive exposure may lead to diminished

kidney function resulting in anuria (cessation of urine production) returns to normal in 2-3 weeks

Dermal exposure has been reported to cause parkinsonian like symptoms and severe burns

Diquat:Signs & Symptoms

Ingestion may cause nausea, vomiting, abdominal pain, and diarrhea

Higher doses (over 3 ounces) may cause digestive tract ulceration, pulmonary edema, loss of consciousness and death

Chlorophenoxyl Herbicides

2,4-D and 2,4,5-T were the active ingredients in “Agent Orange”

2,4,5-T banned in the U.S.2,4-D widely used as an agricultural

herbicideHealth effects of these compounds

remain controversial

2,4-D:Target Organs

Causes peroxisome proliferation hepatocytes in animals

Such proliferations may cause increased DNA damage as a result of oxygen radicals

2,4-D:Signs & Symptoms

Ingestion may lead to:nausea vomiting

drowsiness hypotensionslurred speech abdominal pain hyperventilation renal dysfunction ataxia agitation

pulmonary edema hypoxia

GlycophosphateActive ingredient in RoundupBroad spectrum, non selectiveLow oral toxicity to other mammals,

however human fatalities have been reported form intentional poisoning

Degrades slowly in water

Glycophosphate:Signs & Symptoms

Ingestion may lead to:- pulmonary dysfunction- gastrointestinal irritation- metabolic acidosis- renal failure- cardiac arrest- seizures- coma

Rodenticide Characteristics

Must have agreeable odor and tasteEffective on certain species and/or agesMultiple doses required

- If rats die immediately, other rats will not take the bait.

- Formulations acutely toxic to rats in one dose are usually very toxic to humans.

WarfarinUsed for the control of rats and miceAvailable for household rodenticidesUsefulness is due to ability to cause

vascular injury, resulting in hemorrhagesTeratogen - should not be used by

pregnant womenD-Con, Arthrombine-K, and Panwartin

Vitamin D Related Compounds

Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3)

Hypervitaminosis D interferes with metabolism and causes hypercalcemia

Symptoms may include anorexia, nausea, vomiting constipation or diarrhea

Intoxication may cause mental confusion, loss of memory, and acute renal failure

Ergocalciferol:Signs & Symptoms

Causes mineralization of the heart and kidneys

Renal tubular injuries, pulmonary bleeding, and centrilobular necrosis

Nicotine may cause calcification of cardiac tissues by increasing absorption of calcium

Cholecalciferol:Signs & Symptoms

Increases animal plasma calcium concentrations

Causes a more pronounced toxic response than ergocalciferol

The Final Word on Pesticides

“The dose makes the poison”Proper use of pesticides can benefit

public health, protect food supplies and property.

Improperly used pesticides can poison man and other species.