Environmental Medicine (week 8): Soil Safety
Pesticides, etc.
HISTORY
1972 FIFRA act, Fed Insecticide, Fungicide and Rodenticide Act
4 CLASSES BASED ON LD50
no concern for morbidity, carcinogenesis, etc
I most toxic, LD50 = <5grams, must have danger-poison label, "fatal if swallowed"
II moderately toxic, warning label, LD50 = 5-30g
III slightly toxic, caution LD50<30gm
IV nontoxic
RESOURCES
National Pesticide Info Ctr (NPIC)
in Corvallis at OSU
http://npic.orst.edu/index.html
800-858-7378 for physician consults
EPA
Pesticides and Food
www.epa.gov/pesticidesfood/risks/htm
What's on my Food
www.whatsonmyfood.org
good patient info
INSECTICIDES
to prevent crop damage, infx dz (malaria), nuisance
consider psych factor with desire to eliminate insects
ORGANOCHLORIDES
variety of chem strx with multiple C-Cl bonds
aldrin, dieldrin, chlordant, heptachlor, oxychlor, DDT, DDE, endrin, mirex, trichlorophenol, lindane, etc
DDT & Organochlorides
dichlorodiphenythrichloroethane
tasteless, almost odorless
used in WWII, Vietnam, ag 40-80's
sim to DDE and DDD, together = "total DDT"
MOA: opens Na channels in NS-->creates action potentials-->spasm
little effect on humans: youtube.com/watch?v-gtcXXbuR244&feature=related
no acute toxicity
DDT AND BIRDS
lipophilic POP
bioaccumulates esp in predatory birds, fishing birds, osprey and eagle
inhibits calcium carbonate formation in shells-->weak shells, non-viable crushable eggs
decline in bird species-->Rachel Carson's "Silent Spring" (birds all dead)
bald eagle most famous casualty, 400,000 present but down to 500 in 50's
DDT ban in 1972, Endangered species act 1973, Sig comeback now >20,000 bald eagles, no longer endangered
www.fws.gov/midwest/eagle.index.html
DDT HEALTH EFFECTS
little absolute evidence, most conflicting
two meta-analyses: Lancet 2005 and Envir Health Perspectives, "Pine River Statement" conference summary
Endocrine disruptor-->IR, thyroid, Est receptor fx (preg, miscarriage, menses, early puberty), decr T (sterile)
Neurodevelopmental toxin: effects reflexes, sensory, memory, soc, behavior, intelligence, learning
Carcinogen: liver, panc, 5x breast risk if pre-puberty exposure, leuk, NHL, testicular, prostate
Occupational high dose exposures-->sweat, h/a, N/VD, tremor, siezure, coma, psychosis, dep, anx
Neuro effects not universal
Genetic polymorphisms almost certainly involved
DDT IN FOODS
meat esp fish, dairy, eggs
spinach, lettuce, kale (leafy greens)
ROUTES OF DDT EXPOSURE
food, farming, living near farms
travel or residence in foreign countries (India, China and N.Korea still produce it)
used in many tropical countries
LABS FOR DDT
no standard labs, copmlicated, contact NPIC and EPA
lipid bx, blood, urine, semen, breast milk
ORGANOPHOSPHATES (MALATHION)
OPs used as nerve agents (gas), outlawed as WMDs in 1993, Sarin, VX gas, there are still stockpiles
garlic-like odor
mc pesticide in USA: crops, golf courses, home gardens
used as tx for pediculosis (Ovide)(caution: flammable)
unstable in environment, degraded by sunlight, water, temp
lasts hours-weeks, far better than POPs
FDA requires x time to pass btw spraying and entry into ag field, adherence questionable
social justice issues with migrant farm workers
EXPOSURE routes: all, inhal, digest, derm, phosphate group allows easy uptake by bio systems
MOA: enzyme inhibition (neural, neurotransmitter breakdown)
irreversible acetylcholinesterase inhibition-->prevents breakdown of ACh in synapse
susceptible to oxon formation (convert sulfonyl S= group to carbonyl O= group)
malaoxon is 60-100x more toxic
SX: SLUDGE dt parasympathomimetic fx, h/a, dizz, seiz, coma, anx, lability, insomnia
New link to ADHD, NHANES data, n-1139 kids, 2x ADHD with >median OP levels
LABS: urinary metabolites: DMP, DMTP, DMDTP, DEP, DETP, DEDTP
Genetic polymorphisms influence metabolism
LABS: Blood cholinesterase activity in RBC's best
RBC (True) can be done via LabCorps, NCNM
Butyrylcholinesterase (plasma), aka BCHE psudocholinesterase,
less specific, shows all cholinesterase activity in body
Test strips to apply to food detects ACh-esterase, OPs, carbamates, used in rural developing countries
see science daily
TREATMENT for acute:
RX: ATROPINE IV 1-2mg q15 min til secretions stop (anticholinergic)
consider: bell, datura, hyoscyamus
Rx: Pralidoxime (2-PAM): 30-50mg/kg IV push in 30-60 mins, specific for cleaving OPs from ACh-esterase
best if used immediately
PRYETHROIDS (PERMETRHIN)
raid and OFF bug spray are derivatives
break down easily in environment
mc class of chem insecticides
toxic to fish, cats (low toxicity to humans)
used in crop dusting, does not accumulate, also used in shampoos, pet sprays, scabies TX
NOT a POP
binds strongly to soil
MOA: fixed membrane depoarlization, keeps Na channels open so nerve conduction is not possible
synthetic pyrethrins more potent and durable
usu mixed with enzymes, leads to increased toxicity
HEALTH EFFECTS
acute: burn, irrit, itch, numb
NS: dizz, ha, n, twitch, fatigue, altered LOC, convulsions, coma
Concern: dopaminergic system affected-->parkinson's, neonatal development
for parkinson's consider: rotenone, paraquat
CARBAMAATES (CARBARYL)
aka Urethane
primarily synthetic
aside from pestices used in solvents (polyurethan), medicine (cholinesterases, etc)
Uses: ag, home insecticide, #3 mc insecticide
MOA: cholinesterast inhib
SX: sludge
Longterm exposure: BM toxin, hepatic and renal degen/fatty necrolysis, endocrine disruption, cancer (vasc)
BHOPAL
1984 Bhopal disaster, India, Union carbide
40 tons of Methyl isocyanate, 5200,000 exposed, 25,000 dead
sx dt mix of MIC, cyanide, phosgene
ROTENONE
used for centuries for fishing
extract from tropical legums, piscicide
not absorbed in human GI
disrupts mito fx in fish
link to Parkinson's, NIH Feb 2010 study
www.nih.gov/news/health/feb2011/niehs-11.htm
has been phased out dt envir effects
NEONICONTINOIDS (IMIDACLOPRID)
linked to colony collapse in bees
HERBICIDES
two types: selective (weed killers) and non (clearing area of all veg)
PHENOXY HERBIICDE (2,4D)
selective for dicots
most widely used herbicide in the world
1st commercially developed herbicide
auxin: plant growth hormone causes dicots to overgrow and die
health effects: pretty safe to rats, no link to cancer as of 2007
LINKED: NHL in farmers, ALS, sterility
component of agent orange, used in Vietnam to remove tree cover, dioxin also in there
caused harm to 2-4 million, cancer, 500K birth defects, vets also got some
#4 for causing birth defects
PARAQUAT
nonselective herbicide
undetectable by senses, chems added to help prevent accidental exposure
highly toxic, restricted use, very short half life
increases ROS, prevents photosynthesis
exposure via ingestion, some derm, not much inhalation (worry re "paraquat pot" found false)
suicide method: 2 tsp will do 'er, cheap, widely available in ag communities
SX: inflam, irrit of GI, fibrosis, scarring, N/v/d/pain, pulm edema, SOB, dyspnea, kidney, liver and heart failure, confus, dizz, seiz, coma, death
LINKed to Parkinson's (feb 2010 study)
ATRAZINE
nonselective herbicide
#2 most widely used in US
highly toxic, absorbed thru roots of plants (with water)
inhibits photosynthesis and electron capture, strong ROS
accumulates in soil and ground water
does not bioaccumulate
Ag workers most at risk
mostly in midwest, grain belt, Iowa, Ill, Mo, eastern Neb, upper Mississipi basin, some wherever farming
lots in gulf of Mexico, kills all plant life, "dead zone" size of NJ, no fish or shellfish
HEALTH EFFECTS: premies, birth defects, liver, kidney, heart damage, endocrine disruption esp male
cleared from body in 24-48 hours
ca risk unknown
acts at very low doses
hermophroditic amphibians, 2-3 ovaries in male frogs, 6 testicles, feminization, etc
anatomically female male frogs can viably mate with males pubmed 20194757
http://news.nationalgeographic.com/news/2002/04/0416_020416_TVfrog.html
EPA 2003 insuff to say threat to health
2006 plenty of evidence says threat to health,
2009 EPA changes their opinion (Lisa Jackson director)
GLYPHOSATE (ROUNDUP)
non-selective
#1 most widely used herbicide in US
interferes with aa production
solid powder or liquid
produced since 1970
Monsanto's roundup ready crops 1996, GMOs resistant to glypohsate
soy now 87% roundup ready in US
also: corn, canola, alfalfa, cotton, sorghum, wheat
marker of crop distribution, wind dispersal contamination of organic crops
http://www.nytimes.com/2010/05/04/business/energy-environment/04weed.html?pagewanted=all
HEALTH EFFECTS: cellular toxin, growth inhibotr, toxic to placent, endocrine disruptor (decr aromatase), GI corrosive, hep and renal impair, resp distress, pulm edem, bradycardia, hyperkalemia
not carcinogenic (yet)
FERTILIZERS
contain: nitrogen, phosphorus, potassium, micronutrients
types: conventional and organic
conventional usu made of petroleum and mining byproducts, recycled industrial waste
contaminated with heavy metals, dioxins, PCBs
NITRATES accumulate in well water from ag, 1-3% of US pop exposed to high nitrates
also in veg, meat esp sausages, meds
causes methhemoglobinemia, Fe2+-->3+, hypoxia, esp in infants
well water from well to mix baby formula
tx: methylene blue IV
EUTROPHICATION =overgrowth of algae in water-->blooms
Organic fert works fine
DIRTY DOZEN
www.thedailygreen.com/healthy-eating/eat-safe/dirty-dozen-foods
peach
apple
bell peppers
celery
nectarine
strawberry
cherry
kale
lettuce
grapes
carrots
pear
CLEAN FIFTEEN
onion
avocado
sweet corn
pineapple
mangoes
asparagus
sweet peas
kiwi
cabbage
eggplant
papaya
watermelon
broccoli
tomato
sweet potato
HISTORY
1972 FIFRA act, Fed Insecticide, Fungicide and Rodenticide Act
4 CLASSES BASED ON LD50
no concern for morbidity, carcinogenesis, etc
I most toxic, LD50 = <5grams, must have danger-poison label, "fatal if swallowed"
II moderately toxic, warning label, LD50 = 5-30g
III slightly toxic, caution LD50<30gm
IV nontoxic
RESOURCES
National Pesticide Info Ctr (NPIC)
in Corvallis at OSU
http://npic.orst.edu/index.html
800-858-7378 for physician consults
EPA
Pesticides and Food
www.epa.gov/pesticidesfood/risks/htm
What's on my Food
www.whatsonmyfood.org
good patient info
INSECTICIDES
to prevent crop damage, infx dz (malaria), nuisance
consider psych factor with desire to eliminate insects
ORGANOCHLORIDES
variety of chem strx with multiple C-Cl bonds
aldrin, dieldrin, chlordant, heptachlor, oxychlor, DDT, DDE, endrin, mirex, trichlorophenol, lindane, etc
DDT & Organochlorides
dichlorodiphenythrichloroethane
tasteless, almost odorless
used in WWII, Vietnam, ag 40-80's
sim to DDE and DDD, together = "total DDT"
MOA: opens Na channels in NS-->creates action potentials-->spasm
little effect on humans: youtube.com/watch?v-gtcXXbuR244&feature=related
no acute toxicity
DDT AND BIRDS
lipophilic POP
bioaccumulates esp in predatory birds, fishing birds, osprey and eagle
inhibits calcium carbonate formation in shells-->weak shells, non-viable crushable eggs
decline in bird species-->Rachel Carson's "Silent Spring" (birds all dead)
bald eagle most famous casualty, 400,000 present but down to 500 in 50's
DDT ban in 1972, Endangered species act 1973, Sig comeback now >20,000 bald eagles, no longer endangered
www.fws.gov/midwest/eagle.index.html
DDT HEALTH EFFECTS
little absolute evidence, most conflicting
two meta-analyses: Lancet 2005 and Envir Health Perspectives, "Pine River Statement" conference summary
Endocrine disruptor-->IR, thyroid, Est receptor fx (preg, miscarriage, menses, early puberty), decr T (sterile)
Neurodevelopmental toxin: effects reflexes, sensory, memory, soc, behavior, intelligence, learning
Carcinogen: liver, panc, 5x breast risk if pre-puberty exposure, leuk, NHL, testicular, prostate
Occupational high dose exposures-->sweat, h/a, N/VD, tremor, siezure, coma, psychosis, dep, anx
Neuro effects not universal
Genetic polymorphisms almost certainly involved
DDT IN FOODS
meat esp fish, dairy, eggs
spinach, lettuce, kale (leafy greens)
ROUTES OF DDT EXPOSURE
food, farming, living near farms
travel or residence in foreign countries (India, China and N.Korea still produce it)
used in many tropical countries
LABS FOR DDT
no standard labs, copmlicated, contact NPIC and EPA
lipid bx, blood, urine, semen, breast milk
ORGANOPHOSPHATES (MALATHION)
OPs used as nerve agents (gas), outlawed as WMDs in 1993, Sarin, VX gas, there are still stockpiles
garlic-like odor
mc pesticide in USA: crops, golf courses, home gardens
used as tx for pediculosis (Ovide)(caution: flammable)
unstable in environment, degraded by sunlight, water, temp
lasts hours-weeks, far better than POPs
FDA requires x time to pass btw spraying and entry into ag field, adherence questionable
social justice issues with migrant farm workers
EXPOSURE routes: all, inhal, digest, derm, phosphate group allows easy uptake by bio systems
MOA: enzyme inhibition (neural, neurotransmitter breakdown)
irreversible acetylcholinesterase inhibition-->prevents breakdown of ACh in synapse
susceptible to oxon formation (convert sulfonyl S= group to carbonyl O= group)
malaoxon is 60-100x more toxic
SX: SLUDGE dt parasympathomimetic fx, h/a, dizz, seiz, coma, anx, lability, insomnia
New link to ADHD, NHANES data, n-1139 kids, 2x ADHD with >median OP levels
LABS: urinary metabolites: DMP, DMTP, DMDTP, DEP, DETP, DEDTP
Genetic polymorphisms influence metabolism
LABS: Blood cholinesterase activity in RBC's best
RBC (True) can be done via LabCorps, NCNM
Butyrylcholinesterase (plasma), aka BCHE psudocholinesterase,
less specific, shows all cholinesterase activity in body
Test strips to apply to food detects ACh-esterase, OPs, carbamates, used in rural developing countries
see science daily
TREATMENT for acute:
RX: ATROPINE IV 1-2mg q15 min til secretions stop (anticholinergic)
consider: bell, datura, hyoscyamus
Rx: Pralidoxime (2-PAM): 30-50mg/kg IV push in 30-60 mins, specific for cleaving OPs from ACh-esterase
best if used immediately
PRYETHROIDS (PERMETRHIN)
raid and OFF bug spray are derivatives
break down easily in environment
mc class of chem insecticides
toxic to fish, cats (low toxicity to humans)
used in crop dusting, does not accumulate, also used in shampoos, pet sprays, scabies TX
NOT a POP
binds strongly to soil
MOA: fixed membrane depoarlization, keeps Na channels open so nerve conduction is not possible
synthetic pyrethrins more potent and durable
usu mixed with enzymes, leads to increased toxicity
HEALTH EFFECTS
acute: burn, irrit, itch, numb
NS: dizz, ha, n, twitch, fatigue, altered LOC, convulsions, coma
Concern: dopaminergic system affected-->parkinson's, neonatal development
for parkinson's consider: rotenone, paraquat
CARBAMAATES (CARBARYL)
aka Urethane
primarily synthetic
aside from pestices used in solvents (polyurethan), medicine (cholinesterases, etc)
Uses: ag, home insecticide, #3 mc insecticide
MOA: cholinesterast inhib
SX: sludge
Longterm exposure: BM toxin, hepatic and renal degen/fatty necrolysis, endocrine disruption, cancer (vasc)
BHOPAL
1984 Bhopal disaster, India, Union carbide
40 tons of Methyl isocyanate, 5200,000 exposed, 25,000 dead
sx dt mix of MIC, cyanide, phosgene
ROTENONE
used for centuries for fishing
extract from tropical legums, piscicide
not absorbed in human GI
disrupts mito fx in fish
link to Parkinson's, NIH Feb 2010 study
www.nih.gov/news/health/feb2011/niehs-11.htm
has been phased out dt envir effects
NEONICONTINOIDS (IMIDACLOPRID)
linked to colony collapse in bees
HERBICIDES
two types: selective (weed killers) and non (clearing area of all veg)
PHENOXY HERBIICDE (2,4D)
selective for dicots
most widely used herbicide in the world
1st commercially developed herbicide
auxin: plant growth hormone causes dicots to overgrow and die
health effects: pretty safe to rats, no link to cancer as of 2007
LINKED: NHL in farmers, ALS, sterility
component of agent orange, used in Vietnam to remove tree cover, dioxin also in there
caused harm to 2-4 million, cancer, 500K birth defects, vets also got some
#4 for causing birth defects
PARAQUAT
nonselective herbicide
undetectable by senses, chems added to help prevent accidental exposure
highly toxic, restricted use, very short half life
increases ROS, prevents photosynthesis
exposure via ingestion, some derm, not much inhalation (worry re "paraquat pot" found false)
suicide method: 2 tsp will do 'er, cheap, widely available in ag communities
SX: inflam, irrit of GI, fibrosis, scarring, N/v/d/pain, pulm edema, SOB, dyspnea, kidney, liver and heart failure, confus, dizz, seiz, coma, death
LINKed to Parkinson's (feb 2010 study)
ATRAZINE
nonselective herbicide
#2 most widely used in US
highly toxic, absorbed thru roots of plants (with water)
inhibits photosynthesis and electron capture, strong ROS
accumulates in soil and ground water
does not bioaccumulate
Ag workers most at risk
mostly in midwest, grain belt, Iowa, Ill, Mo, eastern Neb, upper Mississipi basin, some wherever farming
lots in gulf of Mexico, kills all plant life, "dead zone" size of NJ, no fish or shellfish
HEALTH EFFECTS: premies, birth defects, liver, kidney, heart damage, endocrine disruption esp male
cleared from body in 24-48 hours
ca risk unknown
acts at very low doses
hermophroditic amphibians, 2-3 ovaries in male frogs, 6 testicles, feminization, etc
anatomically female male frogs can viably mate with males pubmed 20194757
http://news.nationalgeographic.com/news/2002/04/0416_020416_TVfrog.html
EPA 2003 insuff to say threat to health
2006 plenty of evidence says threat to health,
2009 EPA changes their opinion (Lisa Jackson director)
GLYPHOSATE (ROUNDUP)
non-selective
#1 most widely used herbicide in US
interferes with aa production
solid powder or liquid
produced since 1970
Monsanto's roundup ready crops 1996, GMOs resistant to glypohsate
soy now 87% roundup ready in US
also: corn, canola, alfalfa, cotton, sorghum, wheat
marker of crop distribution, wind dispersal contamination of organic crops
http://www.nytimes.com/2010/05/04/business/energy-environment/04weed.html?pagewanted=all
HEALTH EFFECTS: cellular toxin, growth inhibotr, toxic to placent, endocrine disruptor (decr aromatase), GI corrosive, hep and renal impair, resp distress, pulm edem, bradycardia, hyperkalemia
not carcinogenic (yet)
FERTILIZERS
contain: nitrogen, phosphorus, potassium, micronutrients
types: conventional and organic
conventional usu made of petroleum and mining byproducts, recycled industrial waste
contaminated with heavy metals, dioxins, PCBs
NITRATES accumulate in well water from ag, 1-3% of US pop exposed to high nitrates
also in veg, meat esp sausages, meds
causes methhemoglobinemia, Fe2+-->3+, hypoxia, esp in infants
well water from well to mix baby formula
tx: methylene blue IV
EUTROPHICATION =overgrowth of algae in water-->blooms
Organic fert works fine
DIRTY DOZEN
www.thedailygreen.com/healthy-eating/eat-safe/dirty-dozen-foods
peach
apple
bell peppers
celery
nectarine
strawberry
cherry
kale
lettuce
grapes
carrots
pear
CLEAN FIFTEEN
onion
avocado
sweet corn
pineapple
mangoes
asparagus
sweet peas
kiwi
cabbage
eggplant
papaya
watermelon
broccoli
tomato
sweet potato