Lu- Lecture1 Pesticides

Biomarkers for Pesticide Exposure EH 522 Human Exposure Assessment

Chensheng (Alex) Lu, Ph.D.

Mark and Catherine Winkler Assistant Professor for Environmental Exposure Biology

http://www.hsph.harvard.edu/faculty/ chensheng-lu/ [email protected]

Harvard School of Public Health Boston, MA

Lecture Outlines •  •  •  • 

Pesticides and Public Health, Biomarkers in Environmental Health, No homework for this week, Discussion on an assigned paper.

DDT (dichlorophenyl-trichloroethane) •  Synthesized in late 1800s’, •  Identified as an effective insecticide by Paul Muller in 1940, •  Widely used during World War II, •  Dr. Muller received the Nobel Prize for his work on DDT in 1948, •  DDT was introduced to agriculture afterward.

DDT (dichlorophenyl-trichloroethane) •  An effective pest control chemical with low (acute) mammal toxicity, •  Its persistence and bioaccumulation were not known or disclosed until, •  “Silent Spring”, Rachel Carson, 1962 •  In the 1970’s, DDT use was either banned or restricted in many countries due to bioaccumulation, •  India and other countries still widely use for mosquito and other insect controls, •  In 2006, WHO announced the limited use of DDT in several African countries to battle the resurging mosquito-borne diseases.

DBCP (Dibromochloropropane) •  Developed in early ‘50s by Dow and Shell Chemicals Co. •  Nemagon, trade name, •  Destroys worms that attack banana tree, pineapple and other fruit tree roots, •  Makes the trees grow healthier and longer, •  Approved for sale by USDA in 1961.

Dibromochloropropane (DBCP) •  Nemagon, an instant success within American fruit co., was exported to their plantations in central America and all over the world, •  Plantation workers sprayed and soaked the plants with Nemagon with no personal protection equipment for years.

Warning Sign of DBCP Use •  A third of the workers in a California production plant were declared sterile in 1977. •  Occidental Petroleum Co. was forced to pay millions in compensation. •  US EPA ordered removal of Nemagon from the market in 1977, citing extreme developmental toxicity to humans.

DBCP Use Continued After 1977 •  EPA ordinance to remove Nemagon only valid in US. •  Standard Fruit Co., now known as Dole Food Co., continued to use Nemagon •  As late as December 1978 in Honduras •  Early ‘80s in Nicaragua •  Well into late ‘80s in Philippine plantations

•  With the knowledge of Nemagon caused sterility problem.

The Fact of DBCP Toxicity •  Laboratory tests conducted by the pesticide manufactures in the ‘50s confirmed Nemagon caused testicular atrophy in rats.

DBCP Toxicity from Animals to Humans •  Cancer of the reproductive system, testicular in men, uterine in women •  High numbers of miscarriages •  Kidney failure, diminishing eyesight, weakening bone •  Children of plantation workers the most severely affected •  Congenital deformities

Toxic Harvest

www.mindfully.org/Pesticide/Poisoned-Plantations-Nicaragua.htm

Bhopal, India •  Mid-night, December 3rd, 1984, •  A plume of white vapor streaming from a factory, •  Residents living nearby awoke coughing, choking, gasping, •  Thousands died in a matter of hours, •  A tragedy now acknowledged as the world’s worst-every industrial disaster.

The Culprit? •  Methyl isocyanate •  A chemical used to manufacture pesticide, Carbamate insecticides •  Highly toxic chemical •  Still being used worldwide, not only for producing pesticides but plastics as well

Key Facts •  A catastrophic leak of methyl isocyanate, 27 tons of those, at a Union Carbide pesticide plant killed thousands of people on 12/3/1984, •  150,000 people were left severely disabled, •  Union Carbide’s own documents revealed; •  The plant was designed with “unproven’ and “untested” technology, •  Cut corners on safety and maintenance to save cost, •  None of the 6 safety systems at the plant were functional on 12/3/1984.

A 1962 Union Carbide Ad.

Pesticide Economy 101 •  Product life-cycle is relatively long •  DDT use lasted about 30 years in US,

•  New pesticide is needed because •  Chemical resistance in the field •  Emerging human health concern •  Profit

•  Demands rarely interrupted •  Highly profitable business

Pesticide Economy 101 •  If regulation is becoming a nuisance, either outsourcing the specific agricultural crop or dumping the specific pesticide to less or non-regulated countries/regions, •  North America Free Trade Agreement (NAFTA)

Genetically Modified Crops • 

The sales; •  •  • 

One-stop shopping for farmers, Revolutionized pesticide- and fertilizerfree agriculture, The end of global famine.

Genetically Modified Crops • 

The harvest; • 

“Genetically Modified Weeds” • 

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http://www.npr.org/templates/story/story.php? storyId=13746169

“Bee-B-Gone” • 

Genetically modified corn seeds may be linked to global honeybee Colony Collapse Disorder (CCD)

Genetically Modified Crops • 

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GMO has not and probably won’t deliver the promises that are originally sold to the regulatory agencies and the publics, GMO has added more pressure to the already deteriorating and fragile environment, Not even mention to the consequences of human health.

Genetically Modified Crops •  Modern agriculture often pushes too hard on the environment, •  The outcomes will be interacting with human health via food chain, •  To sustain the agricultural production, we must take note of social and environmental concerns, not just focusing on financial gains.

Unique Characteristics of Pesticide Use •  Pesticide as a group is one of very few chemicals that are designed and manufactured to kill organisms, •  Pesticide is the only toxic chemical that is deliberately applied to the environment, •  Pesticide is the only toxic chemical that the public is willing to pay for uses, •  Pesticide has important public health value.

Organophosphate (OP) Pesticides

Parathion

Malathion

Sarin (nerve gas)

What is pesticide? •  Pesticides used to be natural toxins in a concentrated form, such as copper, arsenic, and pyrethrin, •  As technology improved, contemporary pesticides are being designed and synthesized to; •  Enhance the efficacy and efficiency in killing bugs, weeds, microorganism, etc., •  Quickly degrade in the environment/human body.

What are the pesticides? •  Insecticides

•  Organochlorine, DDT; •  Organophosphates (OP), Malathion; •  Synthetic pyrethroids, Permethrin;

•  Herbicides

•  2,4-D, Roundup, atrazine

•  Fungicides (Fumigant) •  Methyl Bromide;

•  Rodenticides

Pesticide Exposure and Chronic Health Effects  

Neurodegenerative diseases  

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Commonly used insecticides, such as OPs and pyrethroids, acted on central nerve system in insects, Recent environmental epidemiological studies suggest the association with Parkinson’s (OP pesticides) and Autism (pyrethroids)

Pesticide Exposure and Chronic Health Effects    

Neurodegenerative diseases Endocrine Disrupting  

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Due to chemical-structural similarity, several herbibcides and pyrethroids are long been suspected as endocrine disrupting chemicals, Atrazine caused deformities in amphibian

Pesticide Exposure and Chronic Health Effects      

Neurodegenerative diseases Endocrine Disrupting Cancer    

Most of pesticides are not carcinogenic Many cancers thought to be genetic related, are now focusing on the environmental factors    

Gene-Environmental Interaction Epigenetics

Pesticide Exposure and Chronic Health Effects        

Neurodegenerative diseases Endocrine Disrupting Cancer Mostly not yet confirmed !

Pesticide Exposure and Chronic Health Effects  

Mostly unconfirmed, because        

Acute health effect (self-harm) usually not a concern in developed and developing countries, Chronic health end points rarely incorporated in the toxicological studies, Lacking longitudinal exposure assessment at the population levels, Epidemiological studies lack of    

Sufficient scientific evidence for the causation Statistical power to eliminate confounding factors and background noise

Pesticide Human Toxicity - the Dilemma We are being used as the experimental rats for studying the long-term health effects of pesticide uses.

Why Minimizing Pesticide Exposure Critical to Reducing Disease Burden ?  

Its lethal toxicity by design,  

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Its common exposure pattern,    

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The toxicity at the sub-lethal dose unknown; Dietary exposure constitutes the baseline, Modified by periodic elevated exposure from other pathways;

Its likely synergistic interaction with other environmental chemicals in causing adverse health effects.

We Are What We Eat !