Metal-Containing Pesticides
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
M
– rats: 1,850-8,900 mg/kg
– Mice: 7,600-8,200
mg/kg
– Rabbits: 4,450 mg/kg
• Maneb
– Acute toxicity
M = Zn, Zineb
= Mn, Maneb
= Na, Nabam
= Zn+Mn, Mancozeb
• LD50 po > 5,000 mg/kg
in rats and mice
Ethylenebisdisdithiocarbamate fungicides:
an alternative structural form
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
ETHYLENETHIOUREA
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