Pesticide Toxicology
Course Information
Bettina Francis
Entomology Department
bfrancis@uiuc.edu
333-5136
677 Morrill Hall
Barry R. Pittendrigh
Entomology Department
pittendr@illinois.edu
244-0567
518 Morrill Hall
Course Topics
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Classes of Pesticides
– Insecticides
– Herbicides
– Fungicides
– Repellants and Miscellaneous Pesticides
Aspects (of each class and/or selected compounds in each class)
– Synthesis
– Mechanism of action
– Disposition
Major effect on nontarget organisms
– Mammalian toxicity
– Ecotoxicity
– Genetic toxicology
– Reproductive and developmental endpoints
Pesticide Nomenclature
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Structural formula
Generic name
Brand name
CAS number
DDT = dichlorodiphenyltrichloroethane
Verbal Equivalent of Chemical Structure:
p,p’-DDT
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1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane
1,1’-(2,2,2-trichloroethylidene) bis (4-chlorobenzene);
1,1,1-trichloro-2,2bis(p-chlorophenyl) ethane;
1,1,1-trichloro-2,2di (4-chlorophenyl) ethane;
1,1,1-trichloro-2,2di(p-chlorophenyl) ethane;
1,1-bis(4chlorophenyl)2,2,2-trichlorethane;
1,1-bis(p-chlorophenyl)2,2,2-trichlorethane;
2,2,2-trichloro1,1bis (4-chlorophenyl) ethane;
2,2-bis(p-chlorophenyl)1,1,1-trichloroethane.
CAS # 50-29-3
Parathion-ethyl
O,O-diethyl O-p-nitrophenylphosphorothionate
CAS # 56-38-2
Some Brand Names for Parathion-ethyl
• Alkron, Alleron, Corothion, Folidol, Folidol E-65, Genthion,
Geofos, Lethalaire, Niran, Orthophos, Paradusto, Paraspra,
Penncap-E, Thiophos (USSR), Vapophos, Aphemite, Bladan,
Bladan F, Corthione, Danthion, DNTP, DPP, E 605, Ecatox,
Ekatox, Etilon, Fosferno, Fosfex, Fosfive, Fosova, Fostern,
Genthion, Kolphos, Kypthion, Lirothion, Murfos, Niran,
Nitrostigmine, Nourithion, Oleofos 20, Oleoparathion, parathene,
Parawet, Pestox plus, Phoskil, Phosphemol, Phosphenol,
Phosphostigmine, Rhodiatox, SNP, Soprathion, Stathion,
Strathion, Sulphos, Tiofos, Thiophos, Tox 47, Vapophos
1. Insecticides
• Major classes
– Organochlorines
– Organophosphates
– Pyrethroids
• Minor classes
– Plant-derived
– Growth regulators
– Metal-containing
Organochlorine Insecticides
This nomenclature is ambiguous!
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More historical than chemical
All contain carbon & chlorine
Other elements present are hydrogen, oxygen
No sulfur, nitrogen, or halogens other than chlorine
• Primarily insecticides
– 3 subcategories
• DDT and its analogs
• Cyclodienes
– E.g.: dieldrin, chlordane, mirex
• Other
– E.g.: hexachlorobenzene, lindane
DDT
• 1st of the modern insecticides
• Category: organochlorine
• History
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Synthesized by Zeidler, 1874
Insecticidal activity recognized by P Muller, 1939
Critical discovery for Allies in WW II
Production: 300,000 lbs/month by late 1943
DDT and typhus
• 50% mortality before modern antibiotics
• In WW I, 25% of Serbian soldiers died of typhus
• Naples typhus epidemic began 12/43
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305 cases in week of 1/11/44
1,300,000 civilians dusted with DDT at 2 delousing stations
155 cases week of 1/18
Estimated 30,000 lives saved
– Production: 1,700,000 lbs/month by summer 1944
DDT as icon
• 1950s:
– Use and abuse
• 1960s:
– Rachel Carson’s Silent Spring
• 1970s
– Banning DDT: laws vs science
• 1980s - present
– Second-guessing the past
p,p’-DDT
Synthesis of DDT
• Bayer condensation
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2 molecules of chlorobenzene + 1 molecule of chloral hydrate
Stir vigorously
Add excess of concentrated sulfuric acid
Reaction is exothermic
Must be cooled to prevent excess formation of 4chlorobenzenesulfonic acid
• N.B.: 1-step chemical syntheses are cheap & efficient
Synthesis of DDT from chlorobenzene and chloral hydrate:
Physical Characteristics of DDT
• Technical product
– Mixture of isomers
• up to 30% is o,p’-isomer
– Waxy solid of indefinite melting point
• p,p’-DDT
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White, crystalline solid
Melting point 108.5oC
Vapor pressure 1.9 x 10-7 mm Hg at 20oC
Solubility:
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Readily soluble in most aromatic and chlorinated solvents
In acetone: 580 mg/ml (= 580,000 ppm)
In benzene: 780 mg/ml
In water 0.0012 ppm (= 1.2 ppb)
DDT analogs: DDD
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Originally developed by IG Farben
Marketed by Rohm & Haas, 1945
Rapidly metabolized by vertebrates to DDMU
Major product of the anaerobic degradation of DDT
– DDT ---> DDD takes ca 12 weeks
– After 6 months, <1% of DDT has been converted to CO2
Bioaccumulative: used at Clear Lake, CA
DDT Analogs: DDE
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Metabolite of DDT
Not a commercial product
Human dietary exposure:
– 1981 US consumption estimated at 0.001 ppm/day
Air, water levels very low.
May be released from hazrdous waste sites.
Bioaccumulative.
Major cause of avian eggshell thinning
DDT Analogs: Dicofol
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Acaricide (miticide)
Still in use
Minor degradative byproduct of DDT
May contain DDT as impurity
DDT Analogs: Methoxychlor
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Less persistent than DDT
Narrower range of insecticidal activity
Greater estrogenic activity
Still in commercial use but production is decreasing
– Banned in US in 2003
– Banned in EU in 2002
• Considerably more estrogenic than DDT
– Considered a serious endocrine disruptor
DDMU