Download Insecticides and Integrated Resistance Management

Document related concepts

Herbicide wikipedia , lookup

Silent Spring wikipedia , lookup

Phytophthora infestans wikipedia , lookup

Organophosphate poisoning wikipedia , lookup

Pesticide wikipedia , lookup

Pesticide degradation wikipedia , lookup

Toxicology and Integrated Resistance
Environmental Fate and Toxicity
An initial recommendation: Be fair and cautious in what
analogies you use to represent low concentrations ...
Dr. Moneen M. Jones
•Mackay notes that many people like to portray low
concentrations of chemicals as negligible by using
analogies that minimize ...
–1 ppm = 1 inch in 16 miles
–1 ppb = 2 seconds in a lifetime
•...but if a cubic meter of a solid or liquid contains
1028 molecules...
–1 part per quadrillion = 10 billion molecules
–Mackay referred to this as "the enormity of tinyness."
Mackay, D. 1988. On low, very low, and negligible
concentrations. Environmental Toxicology and Chemistry 7:
Concentrations too small to matter?
•A volume of soil 1 acre in area by 1-inch deep
contains 3,120 cubic yards of topsoil.
•At 1 ton per cubic yard, this volume weighs
6,240,000 lbs.
•At an application rate of 0.4 lb a.i. per acre, a
pyrethroid used for seed corn maggot control is
present at 0.064 ppm in the top inch of the field as
a whole and 0.25 insects for a few weeks.
•Mackay also offered some more understandable analogies ... analogies that
can be visualized:
•In a cubic meter of space:
•1 ppm = a sugar cube
•1 ppb = a broken pencil lead
•1 ppt = a grain of salt
•Mackay argued that the significance of low concentrations depends on how
the chemicals in question act in an organism.
•"Disruptives"... low concentrations may be negligible
•"Distributives"... partitioning among media make magnify concentrations
•"Directives" ... if the chemical damages DNA for example, a single or a few
molecules at the "right" place might be enough to cause injury
Why Toxicology?
•Pesticides are poisons, intentionally
Read this.
–They poison non-target as well as target species because their
modes of action are not specific to pest insects and not all insects are pests.
–Humans, other mammals, fish, birds, and non-target invertebrates
(including natural enemies of pests) may be poisoned.
•Lorenz, E.S. 2009. Potential Health Effects of Pesticides.
Covers …
–Hazard = toxicity X exposure. Hazards are reduced by formulating
low-concentration products and low-dust products; applying them to specific
locations; requiring personal protective equipment (gloves, masks, etc.);
imposing re-entry regulations and pre-harvest intervals (PHIs)
–Toxicity may be viewed in different ways: acute vs. chronic; route of
exposure (ingestion, inhalation, or dermal exposure); endpoint (skin or
mucous membrane irritation, death, mutagenicity, carcinogenicity)
•Lorenz, continued
–Signal words based on acute LD50s…
–Pesticide applicators are warned of
symptoms of acute poisoning for insecticides,
fungicides, and herbicides
A “rule” of toxicology often applied to the acute toxicity of substances is that “the
dose makes the poison.” Studies that use laboratory animals are used to estimate the
dose-response relationship for a pesticide, and one common outcome of such studies
is the estimation of an LD50 – the dose that killed 50 percent of the animals in the test
and is likely to kill 50 percent of animals in a similar population.
Toxicity: the ability of a compound to cause injury or
Mammalian Oral
LD50 values for:
LD50 = dose that causes death
to 50 percent of the animals to
which it is administered in
laboratory bioassays.
In general, the insecticides that
have been developed after the
organophosphates and
carbamates have been less
toxic to mammals.
But what about long-term impacts of
chronic exposures?
• Do pesticides cause other effects that may or
may not be related to their primary mode of
action as acute poisons?
–Birth defects?
–Endocrine effects?
•And how should testing for these effects be
Read this.
•Avery, Dennis. 1995. Saving the Planet Through Pesticides and
Plastics. Hudson Institute, Indianapolis. (A biased and unscientific piece
meant to arm the ill-informed with quotes instead of insights … “the
gods’ honest truth is it’s not that simple.” You can forego reading this
… just understand that it’s “out there.”)
•Baier, C. 2000. Saving the Planet Through Pesticides and Plastics: A
Critical Review.
•Whitford, F., et al. 2003. Pesticide Toxicology: Evaluating Safety and
Risk. (A description of
how required toxicological testing of pesticides is done.)
Reasons for concerns about
pesticides in environmental quality
and human health result from a
If a pesticide is at all toxic to non-target
organisms, it’s persistence (buildup over time)
and its likelihood of movement to groundwater
and surface water are important
• Persistence is one determiner of the magnitude of residues in
soil or on foods. Persistence can be represented by
determining a pesticide's half-life. Half-lives in soil for a few
organochlorine and organophosphate insecticides:
•Ethyl parathion
3-10 yrs
7-12 yrs
2-4 years
14 days
30 – 90 days
40 days
Ranking Persistence
–Inorganics such as lead arsenate
–Chlorinated hydrocarbons
–Neonicotinoids (some)
–Neonicotinoids (some)
Rates of Breakdown are dependent on:
•concentration (extremely high concentrations
degrade more slowly)
•temperature and moisture (increasing levels of
either tend to speed breakdown)
•pH (organophosphates especially ... alkaline
conditions speed hydrolysis, even in the spray
•UV light speeds breakdown (especially for
Breakdown products (metabolites) can themselves be
persistent & toxic:
–aldrin to dieldrin; heptachlor to heptachlor epoxide ...
Metabolites are more persistent and more toxic
–Alar (daminozide) to UDMH ... a carcinogen by current
standards (apple story of 1980s)
–aldicarb to aldicarb sulfoxide in watermelons & other
cucurbits treated illegally (metabolite is more toxic than
the original active ingredient) (watermelon story of
•Residues may be carried away from application
sites, often to unwanted destinations.
•Transport in/by water is influenced by
persistence, water solubility, and soil sorption
Soil Half-life of Insecticides and
parathion (methyl)
chlorpyrifos (Lorsban)
terbufos (Counter)
aldicarb (Temik)
carbofuran (Furadan)
carbaryl (Sevin)
permethrin (Pounce Ambush)
esfenvalerate (Asana)
Soil Half-life
3-10 yrs
2-4 yrs
5 days
30-90 days
21-35 days
70 days
30-90 days
10 days
30 days
35 days
60 days
15 days
• In general, the values that trigger some
concern about a pesticide's potential for
environmental transport are a half-life greater
than 21 days, a soil sorption index of 300 to
500 (or less), and a water solubility of greater
than 30 ppm.
• Triggering one or more of these concerns does
NOT mean that a pesticide should not be used
at all; it simply means that uses should be
•So ... certain pesticides end up in ground water and surface
water for specific reasons.
•Compounds most common in groundwater detections have
–old chlorinated compounds
–Aldicarb (a carbamate sold under the trade name Temik)
–the herbicides atrazine, metolachlor, alachlor, and a few
–Neonicotinoids – now and in the future??
•Reasons: persistence, volume of use, solubility, soil sorption.
•Low solubility / high soil sorption do not
prevent surface water contamination
–Pesticides attached to soil particles can
be carried by erosive runoff (or by wind) and
end up in water and aquatic organisms. Such
problems are especially likely for pre-plant
treatments applied to bare soil in the
spring (rainy season).
• Risks of unwanted transport at mixing and loading sites
(and toxic waste sites) are high for all compounds
regardless of sorption, solubility, or normal persistence.
High concentrations outweigh other characteristics.
Some related issues to consider ...
–Locations of agricultural chemical facilities (and
other point sources of various contaminants) in relation
to community water wells
–Location and construction of farm wells and
mixing/loading practices
–"Land-farming" to dispose of contaminated soils
Back to acute toxicity and LD50s
•LOW numbers indicate GREATER toxicity!!
•LD50 values are not complete indicators even for
acute toxicity.
•Toxicity is influenced by route of exposure,
dilution, and combinations with other chemicals.
•Other types of injury (besides death) occur.
•Many individuals are more susceptible than
• Test animals may not accurately represent
•OBVIOUSLY … Environmental toxicity is also an
issue ... toxicity to fish (pyrethroids, rotenone,
many others), bees (carbaryl, some
neonicotinoids, many others), birds (DDT,
Furadan), and plants (lead arsenate, others) are
all concerns.
Chronic toxicity: Pesticides as carcinogens ... many have been
• Cancer tests use maximum tolerated doses (MTD's) as first screen.
Does constant high dose cause different effects than what we
should expect from occasional low doses? Are there threshold
doses below which injury would not occur?
• Ames' bacterial mutagenicity test: Lots of positives among natural
and synthetic compounds. Did this mean all those natural
compounds really are carcinogens?
• Data (relatively few) that exist from animal trials on the
carcinogenicity of natural compounds show about the same
percent positives as animal trials on synthetics. Do the samples
(trials) represent the populations of compounds?
Possible Conclusions
• Ames and others in this camp are wacko, wrong, paid
off, or misdirected.
• Lots of compounds really are carcinogens. (And there's
no need to add more synthetic ones.) OR (And the
synthetic ones are negligible additions with useful
• The way we identify carcinogens is greatly flawed. (So
what's a better way and what do we do until we
improve the protocol?)
Erroneous logic
• Humans evolved in the presence of natural compounds;
they are therefore safer. (Consider that tests of
carcinogenicity are done on rodents and that they too
evolved in the presence of natural compounds). Also
consider that cancer remains for the most part a disease
associated primarily with aging ... how much impact on the
evolution of a species?)
• All known human carcinogens also cause cancer in highdose rodent studies, so all compounds that cause cancer in
high-dose rodent trials must be human carcinogens.
• A ppb just isn't going to cause any effect.
Wiser conclusions
• –Persistent pesticides have caused and continue to cause problems. We
should not allow current and new compounds and use patterns to pose
the same risks.
• –Transport in water, on soil, etc. moves compounds to unwanted sites; at
these sites the pesticides pose health risks or may be more persistent.
Challenge: to identify environmental transport risks of specific
compounds and select chemicals and use patterns that minimize risks.
• –Most insecticides are broad-spectrum poisons that affect humans, other
vertebrates, beneficial insects, etc. Challenge: to develop pesticides with
selective toxicity.
• –We do not know the answers to all the questions about the risks posed
by pesticides.
Sampling, Thresholds, and
Sampling Methods
• Methods of sampling insect densities differ for
specific pests and commodities.
• Those methods include (but are not limited to):
– direct counts of insects on plants or animals, counts
or ratings of plant damage,
– counts in sweep net samples,
– extraction from soil samples,
– aerial assessment of defoliation or other plant
– counts from pheromone traps (and other traps),
Farm-gate economics
• Lots of costs related to pesticides are absorbed outside
the realm of the simple economics of spray costs and
yield in a single field. These include "environmental
• US EPA budgets for pesticide programs, clean-up,
Superfund, etc.
• USGS groundwater monitoring, 1990 = $140 billion.
• State regulatory and Pesticide Applicator Training
• Fish kills & bee kills
• Pest responses... resistance, resurgence, secondary
Many economists would suggest that
• 1. The costs of pesticides plus application underestimate full social
costs, therefore net benefits of pesticide use are overestimated.
(Existing market equations do not incorporate all impacts of
production or pest management [environmental
damage/cleanup, regulatory agencies, etc.]. These external cost
impacts are absorbed outside the commodity's market equation.)
2. But, external benefit impacts are also absorbed (enjoyed)
outside the commodity's market equation. ("Cheap food" and
contributions to the balance of trade [problem here with
agricultural commodities vs. technology]).
3. To remedy market failure, external costs should be
internalized ... by assessment of pesticide fees and taxes (obvious
political problems).
Field or Farm-Gate Economics
• Farmer: "Is this infestation severe
enough to reduce crop yield?" Will
controlling it (preventing the loss)
save more money than the cost of
• Answering these questions to
make a control decision requires
knowledge of the relationship
between pest density and loss in
crop value (damage). The simplest
(but not real) relationship would
be a straight-line graph, but that is
usually inaccurate for several
reasons (discussion to follow
• Pedigo ( summarizes
important components of the relationship between pest densities and
crop values, and the “real” damage curves that result. Some important
• Injury: The effect that the pest has on the crop or commodity.
• Damage: The effect that injury has on man’s valuation of that crop or
• Damage boundary: The damage boundary is the lowest level of injury
that can be measured. This level of injury occurs before economic loss.
Expressed in terms of yield, economic loss is reached at the gain
threshold, and the gain threshold is beyond the damage boundary.
• Direct Pest: cause damage to fruit
• Indirect Pest: cause damage to plant affecting health of plant
• So the damage curve for most
indirect pests (at least theoretically)
might look like this.
• The crop tolerates some infestation
& injury without damage (plants
compensate for the injury or may
even overcompensate); then suffers
minor losses with incremental
increases in pest density (& injury)
(some compensation still occurs);
then a linear phase occurs in the
loss function; finally a leveling off.
• Damage curves like the one are
based on: (1) injury per pest; (2)
damage (yield and therefore $ loss)
per unit of injury.
Economic Injury Level
The economic injury level (EIL) is the
pest density which causes losses
equal to the costs of control.
The economic threshold (ET) is the
pest density at which control is
initiated to prevent a pest
population from reaching or
exceeding the EIL (the pest density
which causes losses equal to the
costs of control).
How do you identify the EIL from
such a graph?
Key ideas: compensation, damage
between pest
density and
• Cosmetics or grade
limits cause abrupt
changes in crop
Static vs. dynamic thresholds:
European corn borer decision-making guide (a dynamic approach)
Related ideas:
Action thresholds, action levels, control thresholds, aesthetic thresholds... all have somewhat vague
derivations, and density-damage relationships may be undefined or poorly defined. These ideas
substitute for a “real” EIL.
• Pests of humans and animals -- economic values?
• Pests on ornamental plants -- aesthetic value?
• Cockroaches in the kitchen cabinets –
• Multiple pests -- related injury or not (includes weeds, pathogens, etc.)
• Pest/weather interactions …
Ease of control of different stages of a pest …
What if a decision must be made before an infestation can be monitored?
All of these complications pose the need for more research to better define sampling methods,
thresholds, and decision-making for insect pest management.
Environmental EILS:
Some researchers have attempted to
assess the environmental risks
associated with different insecticides
and incorporate those risks into the
insecticide costs and use those
calculations in equations to
determine the profit or loss
associated with an insecticide
application. A chapter by Higley and
Peterson is available on the web at:
It includes two tables that illustrate
the different environmental costs
associated with individual
• The “text” for this lecture was “Economic
Thresholds and Economic Injury Levels”
in Radcliffe’s IPM World Textbook
( For links to
chapters that cover a range of specific topics,
click on the “Contributed Chapters” link on the
left side of the home page.
Insecticide Resistance
Questions to answer:
• What is resistance?
• How prevalent is resistance; what are some
important examples?
• How is resistance identified and measured?
• What biological mechanisms confer resistance?
• How can resistance be managed? (Or … Can
resistance be managed?)
Keep in mind throughout this
In resistance, pre-existing mechanisms are selected by insecticide use; this drives
the evolution of resistant forms.
Populations, not species become resistant.
Individuals are born "resistant;" immunity does not develop.
Resistance results from selection pressure. Managing resistance to conventional
insecticides almost always depends upon minimizing pesticide use.
Insecticide resistance is not the same as tolerance (though this terminology is
always debated).
– Low-level resistance is still resistance, not tolerance.
– Species-wide abilities to survive particular insecticides are tolerance, not resistance. (Aphids
are not killed by the insecticide carbaryl (Sevin) … they did NOT develop resistance as a result
of selection pressure by repeated use of this insecticide; they always have been “tolerant” to
this insecticide.)
How prevalent / how important is
• Resistance has been documented ...
– to every major group of insecticides
– in more than 500 insect and mite species
– roughly …
• 56% are crop pests
• 37 % are med/vet pests
• 5 % are beneficial species
Resistance is most common in
• Diptera (flies)(34% of resistant species) …
including house fly, horn fly, and many
• Lepidoptera (moths)(15%)
• Mites (14%)
• Coleoptera (beetles) (13%)
• Homoptera (bugs) (Hemiptera: Homoptera)
Examples include
Western corn rootworm to cyclodienes (organochlorines) (not to any of the soil
insecticides commonly used in the last 30 years … Why not?)
Indianmeal moth to malathion and Bacillus thuringiensis
Red flour beetle to malathion
Horn fly to pyrethroids
House fly to many insecticides
Diamondback moth to many insecticides
Greenhouse whitefly to many insecticides
Tobacco budworm (Heliothis virscens) to many insecticides
Colorado potato beetle to many insecticides
Anopholes mosquitoes to many insecticides
Codling moth to the organophosphates Imidan and Guthion
Corn earworm (Helicoverpa zea) to pyrethroids
(And there are MANY more)
Resistance triggers new pesticide
development, especially for niche
market products
• Colorado potato beetle … for cryolite (an old abrasive),
rotenone, and then neonicotinoids (when they were just a
niche-market product)
• Diamondback moth … for widespread use of Bacillus
thuringiensis (before resistance to it as well) and then
other new insecticides
• German cockroach … for bait stations that use fungal
pathogens, also hydroprene
• Codling moth … Altacor, Assail, Delegate, and Rimon all
follow the failures of Imidan and Guthion
Resistance is identified / measured
in bioassays ...
What allows insects to survive high
doses of insecticides?
• There are 4 broad categories of resistance
Behavior resistance
Reduced penetration
Metabolic Resistance
Target Site Insensitivity
Behavioral Resistance
• A shift in behavior avoids exposure to
insecticides. Examples are controversial … do
they represent shifts in the genetics of behavior
or just survival for long enough (because of
changes in metabolic activity or target-site
resistance) to exhibit avoidance behaviors that
always existed? Examples: red flour beetle,
cockroaches, and horn fly to pyrethroids.
Reduced Penetration
• Usually provides low levels of resistance, most
useful where increased metabolism (metabolic
resistance) provides internal detoxification). The
PEN gene in house flies confers cross resistance
to different insecticides; similar genes appear to
exist in other species. Examples are known from
house fly, certain mosquitoes, tobacco budworm,
and others.
Metabolic Resistance
• Detoxification mechanisms exist in insects anyway
... nonspecific enzymes break down toxic, lipophilic
(fat-loving) compounds into less toxic (usually)
more soluble compounds for excretion.
• Why don't all insects detoxify compounds equally?
– Manufacture of unnecessary enzymes is an energy
expenditure. As a result, resistant individuals may be
less "fit" than susceptible counterparts in the absence
of the pesticide.
– Recessive genes for greater detoxification action are
maintained "without cost" for the species' benefit.
– Realize that although we may have named an enzyme
DDT dehydrochlorinase or aldrin epoxidase, these
enzymes had (have) other functions as well.
Metabolic Resistance Cont…
• The enzymes that detoxify pesticides include monooxygenases (mixed function oxidases, microsomal
oxidases, and cytochrome P-450 dependent oxidases),
hydrolases(including esterases), and transferases
(glutathione-S- transferase).
• One can determine if metabolic resistance is at work
and what enzymes are involved by using synergists ...
chemicals that block specific enzymes responsible for
specific detoxication steps;
– piperonyl butoxide (pbo) inhibits mixed function oxidases,
– triphenyl phosphate (TPP) inhibits carboxylesterase, and
– S,S,S, tributyl phosphorotrithioate (DEF) inhibits esterases.
(Synergists are also used in a few instances to make
insecticides work better ... PBO in house fly sprays is one
Target Site Insensitivity
• The insecticide penetrates the insect cuticle,
it is not metabolized more rapidly, but it still
does not kill the pest ... so the target site is
– Examples: the kdr gene in Diptera reduces
sensitivity of sodium channels to chlorinated
hydrocarbons and pyrethroids.
– Altered acetylcholinesterase gives resistance to
certain organophosphates in the cattle tick, in the
mosquito Aedes albimanus, and in the twospotted spider mite.
– Altered binding sites on the gut wall in some
Lepidoptera result in resistance to Bacillus
thuringiensis .
A single insect may be resistant to
more than one insecticide as a result
• Cross-resistance: One mechanism confers resistance to more
than one insecticide. Examples include kdr resistance to DDT
and pyrethroids in the house fly and certain mosquitoes.
Oxidases, hydrolases, etc. may detoxify more than one
organophosphate or carbamate.
• Multiple resistance: More than one mechanism evolves
independently in response to selection from different
insecticide applications. Examples: Colorado potato beetle,
house fly, tobacco budworm, diamondback moth, green peach
aphid, and certain Anopheles mosquitoes are resistant by
separate mechanisms to 4 or more classes of insecticides.
• In most instances, resistance to a particular insecticide results
from the selection of a single gene. (This conclusion is not
universally true.)
Resistance Management
• … tries to maintain the usefulness of an
• … attempts to manage target pests after
resistance has led to control failures.
• Managing resistance begins with recognizing the
factors that influence resistance development ...
Biological factors that favor resistance
• Short generation time
• Many numbers
• High heterogeneity (genetic variation)
“Operational” factors
• “Operational” factors that favor resistance development:
– Treatments provide prolonged exposure to the insecticide (via
frequent sprays, long residual, or controlled releases)
– Selection pressure is high (high mortality in the treated portion
of the population)
– No refuges exist (for susceptible insects – and their genes – to
– Large areas are treated
• All of the factors listed above intensify selection.
Detecting / Monitoring resistance
• Many papers stress the importance of detecting and
monitoring insecticide resistance. Although monitoring can be
useful, it is important to determine the exact goal of
monitoring and assess whether or not it can be met. Purposes
include ...
– explanation of control failures
– determination of insecticide choice for a single field (field kits)
– determination of the success of resistance management efforts
... have resistance frequencies dropped or stabilized?
– detection of resistance at an early stage so that management
efforts can begin ... This approach is a problem because
statistical probabilities mean that bioassays must contain very
high numbers of insects in order to provide detection before the
momentum of resistance development is too great.
• After the linear relationship between dose and mortality is known, a
diagnostic dose may be used to detect the presence of resistance in the
• Resistance management must begin before
detection efforts confirm that resistance
development is underway. What can be done
in resistance management?
Resistance Management Techniques
• Minimize selection pressure
– to keep susceptible insects alive ... the idea here is that genes for
susceptibility are a valuable natural resource that should be
No unnecessary treatments
Lowest possible effective rates
Shortest effective residual
Local instead of area-wide treatments (including spot treatments)
Preserve untreated refuges
Use other controls whenever possible (cultural practices and host
plant resistance)
Resistance Management Techniques
• Kill the developing resistant population
– High dose strategy (a well-chosen dose to kill rare
heterozygotes) Dose must remain high (happens
only in transgenics) ... what nontarget impacts for
broad-spectrum insecticides?
– Synergists to neutralize resistance (for metabolic
resistance) … but synergists are unstable in UV
– Mixtures or rotations of insecticides ... to kill
those insects that are developing resistance to
one compound by using a different one.
resistance to
Thank you for your time!
Any questions?
Talk dedicated to Ollie Jones, RIP 11/16/13