metal-containing pesticides. metals essential* – zinc – copper – iron – chromium –...
TRANSCRIPT
Metals
• Essential* – Zinc– Copper– Iron– Chromium– Phosphorus– Selenium– Cobalt
• *All metals are toxic in excess.
• Neutral or detrimental– Tin– Bismuth– Boron– Barium– Antimony– *Arsenic– *Thallium– *Lead– *Mercury
• * Designates invariably harmful metals
General Considerations• Elements do not degrade• Environmental accumulation is a
significant risk of continuing use– As in soil of old orchards?
• Bioaccumulation may occur if metal is in a form that can be taken up by plants– Most metals are excluded by most
plants– Cadmium is taken up by some plants
• Environmental presence in soil implies risk of transport into water
• Movement from soil to air, air to soil also occurs
• Environmental transformations may occur– Hg ---> MeHg
• Toxicology– For most metal-containing
pesticides, the toxicity is due to the metal
– Example: • As-containing herbicide,
fungicide will have similar toxicities despite very different structures
– Exception: • Dithiocarbamate fungicides
Barium
• Barium carbonate: BaCO3 – Rodenticide• 20-25% active ingredient in baits• Neurotoxicant
– Human poisoning?• 1 case of mass poisoning• Substituted for flour in pastry
Chromium• Sodium dichromate: Na2Cr2O7•2H2O
– Cotton defoliant– Wood preservative
• Toxicity:– Bronchiogenic cancer suspected– May require inhalation
• Chromium is also an essential element
Copper• Copper sulfate: CuSO4
– Also known as blue vitriol– Fungicide, algicide
• Bordeaux mixture: CuSO4 and Ca(OH)2 – Fungicide and seed treatment
• Very alkaline• Toxicology
– Acute:• Renal failure
– Chronic:• Fatty degeneration of kidneys, liver• Pneumoconiosis from occupational exposure to Bordeaux mixture• Granulomas of lung, liver , kidney
Zinc• Zinc chloride: ZnCl2
– Wood preservative– LD50 :
• po, rat: 2,200 to 19,000 mg/kg • Ip, mouse: 31 mg/kg• Zinc compounds tend to be emetic
• Zinc phosphide: Zn3P2 – Rodenticide– Toxicity is due to production of phosphine (PH3) by stomach acid– Phosphine causes pulmonary and cerebral edema
:
Cadmium• No known biological function• Cadmium chloride: CdCl2
– Turf fungicide• Toxicity
– Acute• Salivation, diarrhea, vomiting
– Chronic• Poor growth, anemia, kidney damage• Itai-itai from dietary exposure
– May be aggravated by Ca and/or vitamin D deficiencies• High blood pressure?• Accumulates in kidneys
– Human poisoning with CdCl2 has not been reported
Mercury• Toxicology
– Major concern for all forms is chronic toxicity– Elemental Hg:
• Little absorption through GI tract• Not absorbed through skin
• Vapors are primary danger– Dyspnea, fatigue, gingivitis, loss of teeth, tremors, irritability– Depression, despondency, lethargy, weakness, coma, death
– Inorganic Hg:• Mercuric chloride: HgCl2
– Fungicide– LD50 37 mg/kg, po, rat
Organic Mercury Compounds
• 1915: – Phenylmercury salts
• HgC6H6
• 1929: – Alkylmercury salts
• Methylmercury, HgCH3
• LD50 ca 30 mg/kg
• NOAEL = 0.5 mg/kg/day for 150 days
• 1960s-1970s - – Hg-containing pesticides banned by most countries
Organic Mercury Compounds• Toxicology
– Absorbed through skin, GI tract– Crosses blood/brain barrier– Little excretion from CNS– Neurological damage is 1st symptom
• CNS• Tremors, loss of peripheral vision, irritability progressing to dementia• Some improvement if exposure ends• Most damage is permanent
– Pregnant women excrete Hg to fetus• Congenital Minamata disease• No repair possible
• Arylmercury compounds– Acrodynia or “pink disease”
Thallium• Rodenticide
– Home uses banned in US in 1975• Toxicology
– Crosses skin, GI tract– Mechanism of action not well understood
• Interferes with intracellular K?• Thallium sulfate, Tl2SO4
• LD50 10.6 mg/kg, rat po• 1/50 of LD50 per day:
– Depilation in 4 months– Death in 6 months
Arsenic• Insecticides
– Paris Green• Copper acetoarsenite
– Cu(C2H3OO)2 •3Cu(AsO2)– used against Colorado
potato beetle, 1865– Scheele’s Green
• Copper arsenite, CuHAsO– NaAsO2
• still used in poison bait against grasshoppers
– PbHAsO4 • used on apples against codling
moths• Used against gypsy moth• 38,000,000 kg in 1942• LD50 in rats, po: 800 mg/kg
• Herbicide– Cacodylic acid: (CH3)2AsO(OH)
• LD50 in rats, po: 830 mg/kg
• Fungicide– Chromated copper arsenate
• wood treatment– introduced 1940s– phased out 2003
• 12x2x6” board contains 27 g arsenic
• 5 Tbs ash contains enough As to kill a 1,100 lb cow
• tastes salty
Human Toxicity of Arsenic• Acute toxicity
– GI tract symptoms• Cumulative toxicity (rats)
– 1.6 mg/kg/day is NOAEL of arsenites– 3.2 mg/kg/day is NOAEL of arsenates
• Mechanism– Increases permeability of capillaries– Decreases blood pressure ---> shock, death
• Skin lesions– Also used therapeutically to clear skin
• Polyneuropathy• Cancer
– Skin• Following ingestion, not topical application
– Lung• Following inhalation only?• Evidence is epidemiological
– People living downwind from copper smelters
Tin• Inorganic tin does not enter body• Organic tin compounds
– RSnX3 – RSn2X2 – RSn3X – RSn4X
– X =• Simple ion• Complex ion
– R =• Alkyl• Aryl
• Trifentin acetate– Introduced 1954 as fungicide– Also used as molluscicide, algicide
• Bioaccumulates in harbor ecosystems– Neurotoxic
• Banned for environmental reasons
Trifentin acetate
Summary
• All metals are toxic in excess• As, Hg, Cd, Pb– have no useful function in living organisms
• Toxicity of metal-containing pesticides is usually that of the metal– Exceptions:• Dithiocarbamate fungicides• Zinc phosphide
Dithiocarbamate Fungicides• Ethylenebisdithiocarbamates– Maneb– Nabam– Zineb
• Dimethyldithiocarbamates– Ferbam– Ziram
Ethylenebisdithiocarbamates
• Zineb: – Acute toxicity
• LD50 po– rats: 1,850-8,900 mg/kg– Mice: 7,600-8,200
mg/kg– Rabbits: 4,450 mg/kg
• Maneb– Acute toxicity
• LD50 po > 5,000 mg/kg in rats and mice
M
M = Zn, Zineb = Mn, Maneb = Na, Nabam = Zn+Mn, Mancozeb
Dimethyldithiocarbamates– Ziram • LD50 po
– rats: 1400 mg/kg– Mice: 480 mg/kg– Guinea pigs: 100-150
mg/kg
Common Features of Dithiocarbamates
• Acute toxicity is low• Depress thyroid function• Common metabolite:
– Ethylenethiourea• Interact with alcohol consumption
– Blocks oxidation of EtOH at acetaldehyde step
– Acetaldehyde accumulates– Disulfiram (Antabuse)
• Used to prevent EtOH consumption by alcoholics
Disulfiram
Developmental toxicity of ethylenethiourea
• Severe developmental toxicity in rats– Craniofacial malformations
• Little activity in mice• Similar pharmacokinetics in both species
Summary• Toxicity of most metal-containing pesticides depends
on the metal• Toxicity of dithiocarbamates does not depend on the
identity of the metal• Dithiocarbamates are– Thyrotoxic– Suspect carcinogens– Their metabolite, ethylenethiourea,
• Is a developmental toxic in rats but not in mice
• Many dithiocarbamates were voluntarily withdrawn by their manufacturers rather than carrying out currently required safety testing