1. Metal-Containing Pesticides

2. Metals Neutral or detrimental Tin Bismuth Boron Barium Antimony
*Arsenic
*Thallium
*Lead
*Mercury
* Designates invariably harmful metals
Essential*
Zinc
Copper
Iron
Chromium
Phosphorus
Selenium
Cobalt
*All metals are toxic in excess.

3. General Considerations
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
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

4. Barium Barium carbonate: BaCO3 Rodenticide Human poisoning?
20-25% active ingredient in baits
Neurotoxicant
Human poisoning?
1 case of mass poisoning
Substituted for flour in pastry

5. Chromium Sodium dichromate: Na2Cr2O7•2H2O Cotton defoliant
Wood preservative
Toxicity:
Bronchiogenic cancer suspected
May require inhalation
Chromium is also an essential element

6. 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

7. 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 :

8. 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

9. 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
LD mg/kg, po, rat

10. 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

11. 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”

12. 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
LD mg/kg, rat po
1/50 of LD50 per day:
Depilation in 4 months
Death in 6 months

13. Arsenic Fungicide Chromated copper arsenate 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

14. 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

15. Tin Trifentin acetate Trifentin acetate Introduced 1954 as fungicide
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

16. 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

17. Dithiocarbamate Fungicides
Ethylenebisdithiocarbamates
Maneb
Nabam
Zineb
Dimethyldithiocarbamates
Ferbam
Ziram

18. 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
LD50 po > 5,000 mg/kg in rats and mice M
M = Zn, Zineb
= Mn, Maneb
= Na, Nabam
= Zn+Mn, Mancozeb

19. Ethylenebisdisdithiocarbamate fungicides:
an alternative structural form

20. Dimethyldithiocarbamates
Ziram
LD50 po
rats: 1400 mg/kg
Mice: 480 mg/kg
Guinea pigs: mg/kg

21. 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

22. ETHYLENETHIOUREA

23. Developmental toxicity of ethylenethiourea
Severe developmental toxicity in rats
Craniofacial malformations
Little activity in mice
Similar pharmacokinetics in both species

24. 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