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:
1-3.

•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

•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. http://pubs.cas.psu.edu/freepubs/pdfs/uo198.pdf.
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…
•Danger/Poison
•Danger
•Caution
–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 death
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.
Pesticide
DDT chlordane methyl parathion chlorpyrifos terbufos malathion aldicarb carbaryl carbofuran permethrin rotenone nicotine sabadilla pyrethrins microbials mg/kg
113-118
457-590
14
135-163
2-5
885-2800
1
850
8-14
430-4000
60-1500
50-60
4000
1200-1500
NA

• Do pesticides cause other effects that may or may not be related to their primary mode of action as acute poisons?
–Cancer?
–Birth defects?
–Endocrine effects?
•And how should testing for these effects be done?

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. http://www.agls.uidaho.edu/etox/resources/book_reviews/Planet.pdf
•Whitford, F., et al. 2003. Pesticide Toxicology: Evaluating Safety and
Risk. http://www.ppp.purdue.edu/Pubs/ppp-40.pdf (A description of how required toxicological testing of pesticides is done.)

•persistence
•transport
•toxicity
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 characteristics.

• 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:
•DDT
•Heptachlor
•Chlordane
•Ethyl parathion
•Chlorpyrifos
•Diazinon
3-10 yrs
7-12 yrs
2-4 years
14 days
30 – 90 days
40 days

•Longest
–Inorganics such as lead arsenate
–Chlorinated hydrocarbons
–Neonicotinoids (some)
•Medium
–Organophosphates
–Carbamates
–Pyrethroids
–Neonicotinoids (some)
•Shortest
–Botanicals
–Soaps
–Microbials

•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 tank)
•UV light speeds breakdown (especially for microbials)

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
1990s)

•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
(KOC)

Compound
DDT chlordane parathion (methyl) chlorpyrifos (Lorsban) terbufos (Counter) aldicarb (Temik)
Soil Half-life KOC
3-10 yrs
2-4 yrs
5 days
--
--
9800
Water
Sol.(ppm)
0.006
0.1
57
30-90 days
21-35 days
70 days
4600
578
28
1
5
6000 carbofuran (Furadan) carbaryl (Sevin)
30-90 days
10 days permethrin (Pounce Ambush) 30 days esfenvalerate (Asana) atrazine alachlor
35 days
60 days
15 days
45
230
10600
5300
100
170
320
40
0.04
0.002
33
242

• 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 appropriate.

•So ... certain pesticides end up in ground water and surface water for specific reasons.
•Compounds most common in groundwater detections have been
–old chlorinated compounds
–Aldicarb (a carbamate sold under the trade name Temik)
–nitrates
–the herbicides atrazine, metolachlor, alachlor, and a few others.
–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

•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 average.
• Test animals may not accurately represent humans.

•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 identified
• 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?
(http://potency.berkeley.edu/pdfs/handbook.pesticide.toxicology.p
df)
• 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?

• 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 roles.)
• The way we identify carcinogens is greatly flawed. (So what's a better way and what do we do until we improve the protocol?)

• 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.

• –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.

• 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 damage,
– counts from pheromone traps (and other traps),

• 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 externalities:"
• US EPA budgets for pesticide programs, clean-up,
Superfund, etc.
• USGS groundwater monitoring, 1990 = $140 billion.
• State regulatory and Pesticide Applicator Training budgets
• Fish kills & bee kills
• Pest responses... resistance, resurgence, secondary pests

• 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).

• Farmer: "Is this infestation severe enough to reduce crop yield?" Will controlling it (preventing the loss) save more money than the cost of control?"
• 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 definitions).

• Pedigo (http://ipmworld.umn.edu/chapters/pedigo.htm) summarizes important components of the relationship between pest densities and crop values, and the “real” damage curves that result. Some important terms/concepts:
• 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 commodity.
• 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.

• 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 boundary

• Cosmetics or grade limits cause abrupt changes in crop value

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.
Complications:
• 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.

• 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:
• http://ipmworld.umn.edu/chapters/ higley.htm
• It includes two tables that illustrate the different environmental costs associated with individual insecticides
• http://ipmworld.umn.edu/chapters/ higley/higley1.htm
• http://ipmworld.umn.edu/chapters/ higley/higley2.htm

• The “text” for this lecture was “Economic
Thresholds and Economic Injury Levels”
(http://ipmworld.umn.edu/chapters/pedigo.htm) in Radcliffe’s IPM World Textbook
(http://ipmworld.umn.edu/). 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.

• 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?)

• http://pesticidestewardship.org/resistance/In secticide/Pages/InsecticideResistance.aspx
• http://en.wikipedia.org/wiki/Pesticide_resista nce

• 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.)

• 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

• Diptera (flies)(34% of resistant species) … including house fly, horn fly, and many mosquitoes
• Lepidoptera (moths)(15%)
• Mites (14%)
• Coleoptera (beetles) (13%)
• Homoptera (bugs) (Hemiptera: Homoptera)
(11%)

• 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)

• 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

• There are 4 broad categories of resistance mechanisms:
– Behavior resistance
– Reduced penetration
– Metabolic Resistance
– Target Site Insensitivity

• 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.

• 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.

• 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.

• 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 example.)

• 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 insensitive.
– 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 .

• 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.)

• … tries to maintain the usefulness of an insecticide.
• … attempts to manage target pests after resistance has led to control failures.
• Managing resistance begins with recognizing the factors that influence resistance development ...

• Short generation time
• Many numbers
• High heterogeneity (genetic variation)

• “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 survive)
– Large areas are treated
• All of the factors listed above intensify selection .

• 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 field.
10 100 1000

• Resistance management must begin before detection efforts confirm that resistance development is underway. What can be done in resistance management?

• Minimize selection pressure
– to keep susceptible insects alive ... the idea here is that genes for susceptibility are a valuable natural resource that should be maintained.
• 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)

• 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 light
– Mixtures or rotations of insecticides ... to kill those insects that are developing resistance to one compound by using a different one.

Thank you for your time!
Any questions?
Blog: http:// bootheelagpestmanagement.wordpress.com/
Twitter: https://twitter.com/bootheelbuglady
Talk dedicated to Ollie Jones, RIP 11/16/13