VPHY8300/Spring 04

Raghubir P. Sharma
Office: College of Veterinary Medicine 292 Phone: 752-2788

Email: RPSHARMA@VET.UGA.EDU

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INTRODUCTION
Pesticide nomenclature, classification, use
Historical perspectives, production and use Intentional toxic agents to the environment Economic impact Ideal properties

Persistence and biomagnification

Public health considerations
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INTRODUCTION (Cont.)
Silent Spring by Rachael Carson
EPA regulation RPAR (Rebuttable presumption against registration) Toxicity evaluation, current guidelines

GLP (Good Laboratory Practice)

Development cost of pesticides
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Insecticides (Pesticides)
Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest (insect, rodent, nematode, fungus, weed, other forms of terrestrial or aquatic plant or animal life or viruses, bacteria, or other microorganisms on or in living man or other animals, which the administrator declares to be pest, and (2) Any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant.
Federal Environmental Pesticide Control Act
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PESTICIDES
Insecticides
Rodenticides Herbicides

Fungicides
Molluscicides

Piscicides
etc. etc.
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Pesticides
Chemical substance used to destroy pests
Economic poisons Intentionally added to the environment Useful by virtue of selective toxicity

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People and pets can be exposed to insecticides

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People and pets can be exposed to insecticides

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Neurotoxic (convulsant) insecticides

Cholinesterase inhibitors Organochlorine

Pyrethrins Pyrethrins Pyrethroids

Organophosphates Dichlorodiphenyl(non-reversible) ethanes (DDT) Carbamates (reversible) Cyclodienes

-cyano Chlorinated benzenes compounds

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Historical
Prehistoric: Sulfur, whale oil, arsenic, nicotine,
chrysanthemum, copper

Early 19th Century: ethylene bromide, ethylene oxide,

carbon disulfide (as fumigants)

DDT: Synthesized by Zeideler, 1874; Patented Mller,

1944 (to Geigy)

Beginning of World War II: DDT, , dinitrocresol, 2,4-D

TEPP: Used as war gas in WW, insecticide in early
1940s, Parathion: Germany 1944
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Economic Impact

Worldwide Harvest Losses

Crop Rice Maize Wheat Potential (10-6t) 716 563 578 Harvest (10-6t) 379 363 437 Weeds % 11 13 10 Disease % 9 10 10 Insects % 28 13 5

Sugarcane 1603
Cotton
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737
42

15
6

19
12

20
16

63

Historic Use of Pesticides

Cumulative number of chemicals

110 100 80 60 40 20 10 1800 1850 1900 1950 2000

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PESTICIDE USAGE IN THE USA

1400 1200

Million lbs/year

1000

Total

800
600 400 200 0

Agricultural

1960

1975

1985

1995

YEAR
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Pesticide Poisoning in California

Mosquito Abatement Arial Applicators Fumigators Firearm, Police Manufacturing Pest Control Agricultural Workers Field Workers Structural Mixers and Loaders Warehouse and Indoors Gardeners, Nurserymen Ground Applicators

0
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50

100

150

Frequency

Ideal Properties of Insecticides

Effective (at low concentrations)
Stable (??) Non-toxic to other species (Selective, not
toxic to pollinators)

Affordable (Cost effective, adequate supply,

competitive in price)

Non-cumulative (Biomagnification is
incompatible with stability)
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Regulatory Aspects
FIFRA FDCA 1947, updated regularly. No pesticide can be marketed unless approved by EPA Miller Amendment Safe limits of additive in foods

Delaney Clause
(No substance in food that is carcinogenic) TSCA 1976 (EPA established 1970) GLP regulations

FIFRA
FEPCA
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Restrictions, RPAR (Rebuttable Presumption against Registration)

Federal Environmental Pesticide Control Act

Basic Requirements of Toxicity Evaluation

Acute
Oral (Rat) Dermal) (Rabbit)

Inhalation (Generally Rat)

Irritation Potential Eye: Rabbit Skin: Rabbit, Guinea Pig Dermal Sensitization (Guinea Pig) Delayed neurotoxicity (Hen)
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Basic Requirements of Toxicity Evaluation

Subchronic
90-Day Feeding Study Rodent (Rat, Mouse))

Non-rodent (Dog)
Dermal (Depending on Use Pattern) Inhalation Neurotoxicity

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Basic Requirements of Toxicity Evaluation

Chronic One- or Two-year Oral Study Rodent (Usually Rat) Non-rodent (Dog) Life-time Oncogenicity Study Reproductive

Multi-generation (Rat, Mouse), Fertility, Reproduction

Teratogenicity (Rat, Mouse, Rabbit)

In-Vitro Mutagenicity and Mechanistic Studies

Pesticide Development and Costs

Life-Cycle
Cumulative $ 1 million 2 million 4 million

Chemical Development, Patent Preliminary Testing and Toxicity Field studies, Production Patent Ends

11 million Safety Evaluation

12-15 million Commercial Use

-10
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10

17

Years

Good Laboratory Practices

Sponsor Personnel Management Study Director QAU Equipment

SOPs
Protocols Final Report
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Good Laboratory Practices

Historical GLPs are good common sense Documentation
n

Archival Records

Uniformity
Replicability
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Occupational Diseases Reported by Pesticides

Chemicals Organophosphates Types of diseases Systemic poisoning

Halog. Hydrocarbons
Miscellaneous

Respiratory
Skin Others

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Surface Area Exposed

Area (M2) Portion (%)
Whole body Face Hands Forearm 1.85 0.065 0.082 0.121 100 3.5 4.4 6.5

Back & neck

Front neck and V
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0.011
0.015

0.6
0.8

Mass Poisoning by Pesticides

Kind of accident

Pesticide involved

Spillage in transport/storage Endrin, dieldrin, parathion

Eating Improper application HCB, mercury Toxaphene, parathion, PCP

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Children poisoned less than 6 years old, 1995-98

(Shannon, NEJM 342, 186-191, 2000) Agents # of children

Cosmetics
Cleaning products Analgesics Plants Cough and cold medicines Foreign bodies Topical agents Pesticides Vitamins Hydrocarbons
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568,856
500,791 354,722 322,991 278,460 256,263 234,997 164,277 151,871 106,265