Health Effects of Pesticides: Health Effects of Pesticides Marylou Verder-Carlos, DVM, MPVM Pesticide Illness Surveillance Program Worker Health and Safety Branch Department of Pesticide Regulation California EPA


Why Talk About Pesticide Toxicity?: Why Talk About Pesticide Toxicity? Evaluate effects of pesticides according to routes of exposure Have a general understanding of pesticide effects to generate questions to ask during a pesticide illness or injury Use expertise on pesticide uses as it relates to its toxicity


How is Information Collected?: How is Information Collected? DFROII or PIR Interviews Medical Records


What Information is Necessary for Documentation?: What Information is Necessary for Documentation? Onset of Symptoms Types and Characteristic of Symptoms Type of Exposure Type of Pesticide


Slide5: Pesticide Type Onset of Symptoms Exposure Individual Symptom Types & Characteristic


Onset of Symptoms: Onset of Symptoms Necessary to evaluate relationship of exposure to illness Necessary to evaluate pesticide effects to exposure Example: Fieldworker developed skin irritation 3 weeks after working in a field sprayed with benomyl. Fieldworker developed skin irritation 1 day after working in a field sprayed with benomyl.


Non-Specific Symptoms and Signs: Non-Specific Symptoms and Signs Rash Flu-like symptoms Dizziness, malaise, respiratory tract irritation Gastrointestinal symptoms Seizures Odor-related effects Not toxicological effects of active ingredient


Pesticide Illness May Mimic Common Medical Conditions: Mild: Upper respiratory tract infection/influenza Food-borne illness Asthma Plant-induced irritant or allergic dermatitis Severe: Cerebrovascular accident Psychiatric dysfunction Heat stroke Pesticide Illness May Mimic Common Medical Conditions


Symptom Characteristics: Symptom Characteristics Allergic Symptoms seen in predisposed individuals who have a history of being allergic to chemicals Most of this information is from the individual or from the doctor who knows of the patient’s history


Slide10: Toxicity of Pesticides Pesticides range in toxicity from virtually harmless to extremely toxic Some are among the most toxic products produced by man


Slide11: Toxicity of Pesticides There are both acute and chronic toxicities associated with pesticides Health effects may be due to any component of pesticide formulations Some effects are as yet unexplored


Pesticides Since WWII: Pesticides Since WWII Through the 60-70s Ops and Carbamates predominated among insecticides Pyrethrins strong but resistance a problem Herbicides The deregistration of 2,4,5-T eliminated the issues of dioxin in herbicides Paraquat remains highly toxic and widely used


Pesticides Since WWII: Pesticides Since WWII Fungicides The main issues are carcinogenicity and a question of metalotoxicity Fumigants: Standard group with little change


Pesticide Groups: Pesticide Groups Fungicides Herbicides Insecticides Others


Fungicides: Fungicides Acute Effects Irritant & allergic dermatitis Chronic Effects Chronic dermatitis Possible carcinogens


Fungicides: Thiocarbamates: Fungicides: Thiocarbamates Related chemicals,Thiram, Maneb and Zineb Sensitization reported in exposed workers 1990, 26 cases of dermatitis among pear harvesters in Washington state, entered field 5 days after application. Residue data from manufacturer stated a 9-day half-life for the chemical Reentry interval increased to 14 days “Antabuse” effects especially when alcohol ingested after exposure


Fungicides: Thiocarbamate reactions: Fungicides: Thiocarbamate reactions Antabuse effect- experience severe flushing reactions with headache, nausea and vomiting if alcohol is ingested shortly after exposure.


Fungicides: Chlorothalonil: Fungicides: Chlorothalonil Itching and hives in redwood nursery worker Chlorothalonil patch test: Local Type I hypersensitivity 1% chlorothalonil open test Systemic Type I reaction


Fungicides: Chlorothalonil: Fungicides: Chlorothalonil Pigmentary Changes Blue-gray pigmentation in antecubital area Positive skin reaction to chlorothalonil Diagnosis: Ashy dermatitis


Fungicides: Chlorothalonil: Fungicides: Chlorothalonil Ashy dermatitis


Fungicides: Sulfur: Fungicides: Sulfur Potent skin irritant Animal experiments equivocal Airway irritant


Fungicides: Sulfur: Fungicides: Sulfur Positive patch test reaction to a sulfur. This was a subject in a study of nursery workers in California. Positive reactions support sulfur-induced allergy.


Fungicides: Sulfur: Fungicides: Sulfur Apparent irritation reaction to a sulfur-malathion mixture plus a sweaty forearm


Fungicides: Benomyl: Fungicides: Benomyl • Studies have shown benomyl to be a potent experimental allergen • Several cases in a nursery implicated benomyl to cause an allergic contact dermatitis


Herbicides: Herbicides Dipyridyl compounds Paraquat Diquat Glyphosate Phenoxy compounds 2,4,5T (2,4,5-T) 2,4 (2,4-D)


Herbicides: Dipyridyl Compounds: Herbicides: Dipyridyl Compounds Paraquat - Gramoxone™ Diquat - Actor ™ Extremely toxic via ingestion LD50 3-5 mg/kg Toxicity Skin, pulmonary Parkinson’s Disease?


Herbicides: Dipyridyl Compounds: Herbicides: Dipyridyl Compounds Hoffer and Teitelman, 1989 Botella et al, 1985


Herbicides: Paraquat: Herbicides: Paraquat Ingestion 1-4 days GI tract edema, ulcers 24-72 hours Hepatocellular injury Acute tubular necrosis 72-96 hours Pulmonary fibrosis


Herbicides: Other: Herbicides: Other • Nitrophenolics: DNOC Elgetol, Dinitrophenol, Dinocap, Dinoseb -well absorbed dermally, orally and are quite volatile - local skin dermatitis, irritating to mucous membranes - irritation, nausea vomiting, dizziness, sweating, thirst Chronic Toxicity: maybe aplastic anemia or peripheral neuropathy (questionable). Clearly an animal carcinogen Persistent: Still contaminates some water wells in California


 Herbicides: Other : Herbicides: Other Glyphosate (Roundup, Glyfonox) Very irritating to mucous membranes Low toxicity orally Not well absorbed dermally Triazines (atrazine, simazine) Most are irritating Low acute toxicity May be associated with some cancers, endocrine disruption


Insecticides: Insecticides Cholinesterase-inhibitors Organophosphates and n-methyl carbamates Pyrethrins and Pyrethroids New insecticides


Insecticides: ChE-Inhibitors: Insecticides: ChE-Inhibitors • Chlorpyrifos, diazinon, guthion, carbaryl methamidophos, aldicarb, malathion - Absorption: variable, but generally good in solution through all routes - Acute toxicity: variable but generally high many class II, some class I pesticides - Chronic Toxicity: neuropathy, CNS changes in severe cases


Slide33: Signs and Symptoms - Nausea, vomiting, diarrhea - Weakness, twitching, paralysis - Visual blurriness, tearing - Confusion, lightheadedness, coma - Bronchial secretions, wheezing, edema - Sweating, salivation, urination Insecticides: ChE-Inhibitors


Insecticides: ChE-Inhibitors: Treatment: Atropine - antagonizes the effect of acetylcholine on receptors - used as a treatment for both OP poisoning and carbamate poisoning Insecticides: ChE-Inhibitors


Insecticides: ChE-Inhibitors: Treatment •2-PAM, Protopam works by displacing the OP from the cholinesterase used only as a treatment for OP poisoning NOT carbamate toxicity Insecticides: ChE-Inhibitors


Insecticides: ChE Inhibitors: Insecticides: ChE Inhibitors Non-ChE effects of OP pesticides Odor health effects Irritant effects Organophosphate-induced delayed polyneuropathy (OPIDP)


Insecticides: Pyrethrins and Pyrethroids: Insecticides: Pyrethrins and Pyrethroids Pyrethrins Natural insecticidal extract Unstable Pyrethroids Synthetic derivatives Used with piperonyl butoxide


Insecticides: Pyrethrins: Insecticides: Pyrethrins Pyrethrins -Low systemic toxicity. -In massive ingestion-seizures. -Respiratory sensitization -asthma -Common symptoms: - Paresthesia (burning numbness of lips and hands) - Allergic dermatitis


Insecticides: Pyrethroids: Insecticides: Pyrethroids Use increasing Examples of use Structural & agricultural Pet flea control Pediculicide Vector control West Nile virus Aircraft “disinsection”


Insecticides: Pyrethroids: Insecticides: Pyrethroids


Insecticides: Pyrethroids: Insecticides: Pyrethroids West Nile Virus prevention spraying in North Carolina West Nile Virus spraying in New York


Insecticides: Pyrethroids: Insecticides: Pyrethroids • Health Effects Skin - Paresthesia, dermatitis Respiratory - Rhinitis Systemic - Dizziness, headache - Fasciculations, seizures, - Hormonal disruption in vitro


Insecticides: Pyrethroids: Insecticides: Pyrethroids Treatment Decontamination Vitamin E cream Symptomatic therapy Remove from further exposure if needed


New PesticidesReceptor Agonists: New Pesticides Receptor Agonists Chloronicotinyls/Neonicotinoids: Admire®, Provado®, imidacloprid; Assail®, Rescate®, acetamiprid; Platinum®, Actara®, thiamethoxam; Calypso®, thiacloprid Phenylpyrazoles: A broad spectrum neurotoxin that works as a GABA antagonist. Fipronil® Oxidiazines: Neurotoxic sodium channel blocker. Avaunt® Pyrroles and Pyridazinone: Uncouple Oxidative Phosphorylation e.g. Pyridaben (Pyramite®)


New Mechanisms of Actions for Insecticides: New Mechanisms of Actions for Insecticides Buprofezin: a chitin synthesis inhibitor (Applaud® Insect Growth Regulator) Methoxyfenozide: accelerate molting (Intrepid®) Pyriproxyfen: a juvenile hormone that suppresses embryogenesis (Various products such as Adams flea and tick spray® etc) Azadirachtin: From the Neem tree, (NEEMIX®, AZA-DIRECT®, ECOZIN®, AGRONEEM®) disrupts insect molting


New Mechanisms of Actions for Insecticides: New Mechanisms of Actions for Insecticides Spreading Disease Among Insects Bacillus thuringiensis toxins Paralyzes larval gut Fungal Insecticides Causes fungemia and death


Fumigants: Fumigants Wide mixture of poisons Most, acutely toxic to all life forms Most are acutely irritating Most are acute neurotoxins Most will cause shortness of breath, headache, dizziness and mucous membrane irritation


Fumigants: Fumigants Halogenated hydrocarbons Methyl bromide Ethylene dibromide, DBCP Inorganic compounds Sulfuryl fluoride Pro-fumigants Metam sodium Metal phosphides Aluminum, Zinc, Magnesium


Fumigants: Methyl Bromide: Fumigants: Methyl Bromide High vapor pressure Heavier than air Odorless Chloropicrin added Toxic mechanism Tissue methylation


Fumigants: Methyl Bromide: Fumigants: Methyl Bromide Acute Effects: Vesicant Blistering dermatitis Lower respiratory toxicant Delayed pulmonary edema Central nervous system depressant Usual cause of death


Fumigants: Methyl Bromide: Fumigants: Methyl Bromide Phase Out Ozone depletion Exemptions Critical agricultural uses Pre-shipment & quarantine Emergency uses No “ideal” substitute


Fumigants: Sulfuryl Fluoride: Fumigants: Sulfuryl Fluoride Pulmonary Dyspnea, cough, delayed pulmonary edema, fatal hypoxia Renal CNS Weakness, nausea, vomiting, restlessness, muscle twitching, seizures


Fumigants: Metam-sodium: Fumigants: Metam-sodium Hydrolyzes to mixture of irritants Health effects Irritant dermatitis Reactive airways dysfunction syndrome/asthma


Fumigants: Metam-sodium: Fumigants: Metam-sodium Metam-sodium applied to carrot fields Illness reported among School children Workers


Fumigants: Metam-sodium: Fumigants: Metam-sodium MITC detected at school, beyond 500 foot buffer zone Workers required to monitor field for odor


Fumigants: Phosphide Compounds: Fumigants: Phosphide Compounds Metal phosphides hydrolyze Aluminum, zinc, magnesium Phosphine Colorless, fish/garlic odor Highly explosive, corrosive Rapidly oxidizes to phosphoric acid


Fumigants: Phosphine: Fumigants: Phosphine Illness Syndromes May resemble viral syndromes Pulmonary toxicity CNS toxicity Multi-organ failure


Fumigants: Chloropicrin: Fumigants: Chloropicrin Characteristics Colorless, slightly oily liquid with intense pungent odor Heavier than air


Fumigants: Chloropicrin: Fumigants: Chloropicrin Now used as a fumigant (at 100% or in 33-50% combo with methyl bromide Nematicide for soil Insecticide for stored grain Currently used as a warning agent for other fumigants such as methyl bromide and sulfuryl fluoride Causes lacrimation and mucous membrane irritation at relatively low concentrations


Fumigants: Chloropicrin: Fumigants: Chloropicrin Signs and Symptoms Eyes: tearing Pulmonary: Cough, shortness of breath, wheezing, pleuritic chest pain, bronchitis, pneumonia, pulmonary edema Neurologic: headache, nausea, vomiting, vertigo, fatigue Skin: Irritation


Fumigants: Chloropicrin: Fumigants: Chloropicrin Diagnosis: History, Exposure history Physical examination Management No specific antidote Treatment is supportive care Decontamination procedures (flush eyes and skin)


Slide62: Other Pesticides:Rodenticides Mostly anticoagulants Generally very low acute toxicity Not well absorbed except by mouth Bleeding rare in humans May be present in rodent feces and so persist after rodenticide is removed.


Other Pesticides: Disinfectants and Antimicrobials: Other Pesticides: Disinfectants and Antimicrobials Sodium hypochlorite Isopropyl alcohol Gluteraldehyde, formaldehyde Quaternary ammonium compounds Other Mixtures


Other Pesticides: Disinfectants and Antimicrobials: Other Pesticides: Disinfectants and Antimicrobials Acute Asthma exacerbation, bronchitis Chronic: RADS Treatment Oxygen, bronchodilators


Other Pesticides: Propargite: Other Pesticides: Propargite Omite™ Acaricide Contact dermatitis Sustained-release propargite Severe dermatitis with scarring


Other Pesticides: Deet: Other Pesticides: Deet Skin Irritation Contact urticaria CNS Seizures, encephalopathy Children < 5 years High dose/concentrations


How Big is the Problem? How many acute poisonings? : How Big is the Problem? How many acute poisonings? In US 10-20,000 per year World Wide 1-3 million illnesses and 200,000 deaths Counting all cases maybe 25 Million illnesses Studies show enormous underreporting world wide


Pesticide Illnesses in California 1999-2003: Pesticide Illnesses in California 1999-2003


Pesticide Illnesses in Sonoma County, 1999-2003: Pesticide Illnesses in Sonoma County, 1999-2003