PESTICIDES Defined as any substance or mixture of substances deliberately added to the environment and intended for preventing, destroying,

, repelling or mitigating pests Play a major role in the control of vector-borne diseases, which represent a major threat to health of large human populations Example: In 1942, DDT played a promising role in controlling vector-borne diseases. However, because of its bioaccumulation in the environment and its effects on bird population, DDT was banned in 1970s. IMPOTANCE OF PESTICIDES Allow the production of abundant, inexpensive and attractive fruits and vegetables, as well as grains (i.e. herbicides) Control of vector-borne diseases (i.e. insecticides and fungicides) BASIC TOXICOLOGY TESTING REQUIREMENTS FOR PESTICIDE REGISTRATION ANIMAL SPECIES Rat, mouse, guinea pig, rabbit Rabbit rat, guinea pig Guinea pig Rabbit Bacteria, mammalian cells, mouse, rat, Drosophila Rabbit, rodent Rat, mouse Rat Rat, dog Rat, mouse Rat Rat

CHAPTER 22 : TOXIC EFFECTS OF PESTICIDES

TEST

Acute lethality Dermal irritation Dermal sensitization Eye Irritation Acute delayed neurotoxicity Teratogenicity 2- to 4-week toxicity study 90-day toxicity study Chronic toxicity study Oncogenicity study Reproductive/fertility study Developmental neurotoxicity study

INSECTICIDES ORGANOPHOSPHORUS COMPOUNDS CARBAMATES PYRETHROIDS ORGANOCHLORINE COMPOUNDS

 OTHER INSECTICIDES ROTENOIDS, NICOTINE, AVERMECTINS Organophosphorus compounds Includes phosphates, phosphorothioates, phosphoramidates and phosphonates Inhibit AChE and NTE TOXICITY Dermal toxicity Cholinergic syndrome Respiratory failure Intermediate syndrome OPIDP Neurobehavioral disorders ANTIDOTE Alkaline soap Atropine Pralidoxime Diazepam Carbamates Derived from carbamic acid and N-methylcarbamates Include carbaryl and aldicarb Reversible inhibition of AChE and NTE TOXICITY Cholinergic syndrome Embryotoxicity/Fetotoxicity ANTIDOTE Atropine Pyrethroids Natural ( flower heads of Chrysanthemum cinerariaefolium) and synthetic derivative Alter the normal function of insect nerves by modifying the kinetics of voltage-sensitive sodium channels Ex. Type I (Allethrin), Type II (Deltamethrin) TOXICITY Paresthesia (reversed by Vitamin E) Tremors and seizures Slight liver enlargement Increased rate of lymphoma incidence Organochlorine compounds 1. DDT Activates Na channels TOXICITY Motor unrest Hypersusceptibility to stimuli

 Paresthesia Confusion Hepatotoxicity 2. Hexacholorocyclo-hexanes and Cyclodienes Inhibit GABA-gated chloride channels Lindane; aldrin, endrin, heptachlor, toxaphene TOXICITY Convulsions Rotenoids Inhibit the mitochondrial respiratory chain by blocking the electron transport at NADH-ubiquinone reductase TOXICITY Tachycardia and tachypnea Clonic and tonic spasms Muscular and respiratory depression Nicotine Activates the nACh receptors TOXICITY N&V Muscle weakness Respiratory effects Headache Lethargy Tachycardia Green tobacco sickness Avermectins Ivermectin, Abamectin Activates the glutamate-gated chloride channels TOXICITY Hyperexcitability Tremors Incoordination Ataxia Coma-like sedation INSECT REPELLANTS DEET No significant toxicity to humans after subchronic toxicity and neurotoxicity studies HERBICIDES CHLOROPHENOXY COMPOUNDS BIPYRIDIL COMPOUNDS CHLOROACETANILIDES TRIAZINES

 PHOSPHONOMETHYL AMINO ACIDS Chlorophenoxy compounds Auxin growth regulator 2,4-dichlorophenoxyacetic acid TOXICITY Vomiting, burning of the mouthm, abdominal pain, hypotension, myotonia, coma Peripheral neuropathy and neurobehavioral alterations Non-Hodgkins lymphoma, soft-tissue sarcoma Bipyridil compounds Paraquat, diquat Cell membrane disruptors TOXICITY Alveolar edema, anoxia, aveolar fibrosis Cataract N&V, diarrhea, mouth and esophageal ulceration, decreased renal function and neurologic effects Chloroacetanilides Alachlor, acetochlor, metolachlor Carcinogenic Triazines Inhibit photosynthesis Atrazine TOXICITY Decrease body weight Clastogenic Phosphonomethyl amino acids 1. Glyphosate Inhibit 5-enolppyruvylshikimic-3-phosphate Roundup TOXICITY GI bleeding, hypotension, pulmonary dysfunction, renal damage 2. Glufosinate Inhibit glutamine synthetase TOXICITY Developmental toxic effects GI effects, impaired respiration, neurologic disturbance, CV effects FUNGICIDES CAPTAN AND FOLPET Eye irritants, mild dermal irritants, carcinogenic DITHIOCARBAMATES Maneb, Ziram, Zineb. Mancozeb

 Inhibits aldehyde dehydrogenase Hypertrophy and hyperplasia of thyroid follicular cells INORGANIC AND ORGANOMETAL FUNGICIDES Copper Sulfate Triphenyltin acetate May cause reproductive and endocrine toxicity Organic mercury compounds (Methylmercury) RODENTICIDES FLUOROACETIC ACID AND ITS DERIVATIVES Sodium fluoroacetate, fluoroacetamide CNS and CV toxicity ANTICOAGULANTS Coumarin derivatives Inhibit Vitamin K epoxide reductase FUMIGANTS METHYL BROMIDE Symptoms of respiratory, GI and CNS toxicity 1,3-DICHLOROPROPENE Skin redness and necrosis SULFUR Dermatitis, cerebrocortical necrosis (polioencephalomalacia)

CHAPTER 22: TOXIC EFFECTS OF PESTICIDES

HANNIAH A. MACASIPOT BSP4A DR. NAYA O. CHACON January 25, 2013