Transcript Pyrethyroids

Pyrethroids
+
Piperonyl butoxide
=
Laurel Fink
Biol 564
April 29, 2008
Pyrethroids and Usage History
• Diverse group of insecticides
(1,000+)
• Many developed in 1970’s and 80’s
by Bayer AG Co.
• Derived from pyrethrins; natural
compounds produced by
chrysanthemum flowers (C.
cinerariaefolium and C. cineum
• Pyrethrins will paralyze insect;
animal will recover (enzyme
detoxification)
• Pyrethroids are synthetic esters
derived from pyrethrins; engineered
for insect death, “knockdown” effect
• Synthetic modifications (addition of
synergists) make these compounds
more toxic to organisms, less
degradable in environment
Pyrethroid
Structures
All pyrethroids have an acid moiety, a
central ester bond, and an alcohol moiety
Permethrin
• Pyrethrins are esters of
chrysanthemic (I) or pyrethric
(II) acid; have been
synthetically modified into
complex mixture of isomers
• Type 1 and 2 pyrethroids
• Very lipophillic, low water
solubility
• Structure of compound (I or II)
has different effects and
associated poisoning
symptoms
• Isomerism around the
cyclopropane ring greatly
influences toxicity
Mode of entry into
aquatic
environment
• Spray drift; pyrethroids often applied
aerially and can contaminate nearby
waters
• Runoff from fields, wastewater from
manufacturing facilities
Reactivity/Speciation in Water
• Rapidly absorbed to particulate matter in water due
to high lipophillicity/low solubility--> absorbed state
less bioavailable to organisms
• Half life for pyrethroids in aquatic medium has been
reported between 19 hours (permethrin in pond
water, Rawn et al., 1982) to 13.5 weeks (fenpropathrin in
distilled water, Takahashi et al., 1985)
• Most pyrethroid half lives in water range from 1-2
days
• Its speciation varies greatly with compound’s
structure, exposure to sunlight, and pH, temperature,
and salinity of water medium
Mode of Entry into Organisms
• Since pyrethroids are highly lipophillic, will
readily be absorbed through the gills of
aquatic animals
• In mammals, toxicity occurs when ingested,
not readily absorbed through skin
Mode of Toxic Interaction:
Neurotoxicity
• Acute neurotoxicity is
caused by binding to sodium
channels--> slows down its
activation and inactivation
properties which leads to a
hyperexcitable state
• A normal action potential is
converted into double or
continuous discharges in
nerve and muscle
• Current duration dependant
on pyrethroid structure;
action stereospecific
• Insect sodium channels 100x
more susceptible than
mammals
Other Toxic Interactions
• Most pyrethroids stimulate protein kinase Cdependant protein phosphorylation (channel
activity modulated by phosphorylation state)
• Antagonism of GABA-mediated inhibition
(seizures)
• Enhancement of noradrenalin release
• Direct actions on calcium or chloride ion
channels (type II only)
• Type II pyrethroids produce a more complex
poisoning syndrome and act on wider range
of tissues
Toxicity to Aquatic Life-- Fish
• Pyrethrins and pyrethroids are extremely toxic to fish,
numerous aquatic invertebrates, can also be
accumulated in aquatic plants
• Will bioconcentrate on and strongly absorbed to gill
tissue; fish seem to be deficient in enzyme that
hydrolyses pyrethroids
• Deltamethrin is most toxic pyrethroid for fishes,
96LC50 for rainbow trout is 1 ug/L, for bluegill and
lake trout, less than 1 ppb
• Sub lethal effects include damage to the gills and
behavioral changes (including accelerated respiration,
loss of movement coordination, convulsions, etc)
Toxicity to Aquatic
Life-Inverts
• Most LC50 values for aquatic invertebrates
less than 1 ppb (similar to LC50’s for target
species such as mosquito larvae)
• These include surface-dwelling insects and
crustaceans, such as mayfly nymphs (most
sensitive), zooplankton, lobster, and shrimp
• At non-lethal concentrations, most have
significant behavioral changes, such as ability
to respond to tactile stimuli
Metabolism and Breakdown
• Biological activity destroyed by ester
hydrolysis, major route, creates oxidative
metabolites
• Oxidative reactions catalyzed by cytochrome
P450 (CYP) enzymes in all animals (CYP6
family important for insects)
• Is thought that insecticidal properties of
pyrethroids terminated by oxidative
metabolism
Defense Strategies/ Detox
• Resistance to pyrethroids due to
detoxification by CYP
monooxygenases
• Resistance associated with
elevated CYP activity
• Pyrethroid resistance in
mosquito larvae recorded
worldwide; permethrin-resistant
strain recently isolated (2007)
with 1300-fold resistance
• This ISOP450 enzyme
mechanism only present in
larval stage, adults not resistant
Bibliography
•
•
•
•
•
•
•
•
Akerblom, N. et al. 2007. Deltamethrin toxicity to the midge Chironomus
riparius-- Effects of exposure scenario and sediment quality. Ecotoxicology and
Environ. Safety. 70: 53-60.
Go, V. et al. 1999. Estrogenic potential of certain compunds in the MCF-7
human breast carcinoma cell line. Environ. Health Perspectives. 107:3.
Hardstone, M.C., et al., 2007. Cytochrome P450 monooxygenase-mediated
permethrin resistance confers limited and larval specific cross-resistance in the
southern house mosquito, Culex pipiens quinquefasciatus. Pesticide Biochem
and Physio. 89:175-184.
Ray, David E. and Fry, Jeffery R. 2006. A reassessment of the neurotoxicity of
pyrethroid insecticides. Pharmacology and Therapeutics. 111:174-193.
Ross, M. K. et al., 2006. Hydrolytic metabolism of pyrethroids by human and
other mammalian carboxylesterases. Biochem. Pharmacology. 71:657-669.
Sanchez-Fortun, S., et al. 2004. Comparative study on the environmental risk
induced by several pyrethroids in estuarine and freshwater invertebrate
organisms. Chemosphere. 59:553-559
U.S. Department of Health and Human Services. 2003. Toxicological Profile for
Pyrethrins and Pyrethroids. Updated 9/2003.
http://www.atsdr.cdc.gov/toxprofiles/tp155.pdf
Velisek, J. et al. 2006. Effects of deltamethrin on rainbow trout (Oncorhynchus
mykiss). Environ. Tox. and Pharmacology