Pesticide Laws, Labels, Safety and Poisoning

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food Drug and Cosmetic Act are the cornerstones of pesticide product regulations. These regulations initially were concerned with pesticide ingredients. In 1947, changes to these regulations were added to include amendments to suspend and cancel pesticides but also included registration of pesticides under protest. Some milestones in current regulations are discussed below.

In the 1950s, the Delaney Clause was included in the Federal Food Drug and Cosmetic Act. This clause prohibited the formation of any food additive regulation that would allow residues of any pesticide that has been tested to produce cancer when consumed by humans or test animals in or on processed food or feed. 

In the early 1960s, the first major problem in the United States (U.S.) unfolded about potential cancer-causing active ingredients in food occurred. The crop of concern was cranberries and the active ingredient was aminotriazole.

During the late 60s the book Silent Spring, authored by Rachael Carson, was published. Although generally considered overstated, this publication brought the use of these chemicals into public light, heightened environmental concern, and changed the use of pesticides in the United States forever. More or less, as a result the USDA canceled the use of DDT in the United States. Substitutes for DDT were the relatively toxic organophosphates. As a result the need developed that individuals applying these materials would do so in a competent manner.

The Environmental Protection Agency (EPA) was created as a result of reorganization of the federal government in 1970. Pesticide regulatory activities including those dealing with registration of pesticide product and approval of their labels were transferred from the Department of Health, Education, and Welfare and the United States Department of Agriculture (USDA) to the newly created Environmental Protection Agency. The newly created agency soon canceled the use of DDT.

In 1972, the current version of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was passed by Congress. The Act did the following:

1. It defined a pesticide as any material or mixture of materials that are intended to kill, repel, or control a pest or to regulate the growth of a plant.

2. It developed Restricted-Use Pesticides, namely those that can be used by or under the direct supervision of a Certified Applicator. Restricted-Use Pesticides are those that have a greater chance of causing adverse impacts to humans and the environment.

3. Created an Applicator Certification Program (including state certification plans).

4. It standardized pesticide labels so that they include: Brand Name, Use Classification (Restricted Use or Non-restricted Use) Ingredient Statement, Net Contents Statement, E.P.A. Registration Number, E.P.A. Establishment number, Statement of Practical Treatment (First Aid), "Keep Out of Reach of Children", Precautionary Statements (Hazards to Humans and Wildlife), Directions for use.

5. Made the pesticide label the law. All users and sellers must adhere to all statements on the label. It is also illegal to make available restricted use pesticides to non-certified personnel.

6. Allowed states to administer equal or more stringent programs under supervision of the EPA. All 50 states now participate.

Part I: Pesticide Labels, Content and Safety

The pesticide label is an extremely expensive piece of paper and takes dozens of years or more to develop the information required to attain federal and state registration of a product. The information found on a pesticide label represents the research, development, and registration procedures that a pesticide product must have undertaken prior to reaching the market. This frequently costs many, many millions of dollars to the manufacturer. The United States Environmental Protection Agency and in many cases individual states (including California) require a pesticide developer to submit massive amounts of data based on up to 150 tests prior to that product's approval for use. These tests include toxicity, environmental persistence, and many other factors that may affect how the pesticide will be safely and effectively used. The culmination of this information is used to develop the pesticide label.

To the manufacturer, the label is the product's Federal and state clearance to sell the product. It also represents the manufacture safety line. To the EPA and various states, the label functions to control the distribution, storage, sale, use, and disposal of the product. From the buyer concern, the label should be considered the main source of information on how to use the product correctly, legally, and safely. 

The content on label is composed of 4 primary major categories, namely safety, environmental, product, and use. This publication discusses the contents of these categories and provides interpretations. For the purpose of this course we will be concerned with safety, the environment and use.

CHILD HAZARDS WARNINGS

The front panel of all pesticide labels must carry the statement, "KEEP OUT OF REACH OF CHILDREN." Poisoning is a major cause of injuries to children. According to the American Association of Poison Control Centers, pesticide exposure incidents occur in greater frequency to children under the age of six years than to older children, teens, and adults on an annual basis. It is well-reported that infants and small children are considerably more sensitive to these toxicants and even inactive ingredients in pesticides than are adults. An infant’s brain, nervous system, and other organs are still in the process of developing well after birth. When exposed to these chemicals, their immature liver and kidneys are not as effective in removing pesticides from the body as are these organs in adults. It is also commonly suggested that babies and young children may also be exposed to more pesticide toxicants than are adults as they breathe faster and have more skin surface in relation to their total body weight. Children frequently spend more time closer to the ground, touching baseboards and lawns where pesticides may have been applied. Small children commonly eat and drink more relative to their body weight than adults. Young children characteristically put their fingers, toys, and other objects into their mouths.

SIGNAL WORDS
 
A signal word is displayed in large letters on the front of the label to indicate approximately how acutely toxic the pesticide is to humans. The signal word is based on the entire contents of the product including formulation and not the active ingredient alone. It takes into account the inert ingredients. The signal word does not indicate the risk of delayed or allergic effects. All highly toxic pesticides that are very likely to cause acute illness through oral, dermal, or inhalation exposure have DANGER as their signal word and will carry the words covering Statement of Practical Treatment

The labels covering all highly toxic pesticides (signal word DANGER, Category I) are required to provide information aimed at medical professionals in the case of exposure. Examples of wording found on labels are: 

  • "If swallowed: Immediately induce vomiting by touching back of throat with finger. Drink 1 or 2 glasses of water and induce further vomiting. Call a physician or poison control center immediately." 
  • “If in eyes: Hold eyelids open and flush with a steady, gentle stream of water for 15 minutes. Get medical attention." 
  • "If on skin, wash skin with soap and water. Get medical attention." 

In addition on this part of the label antidotes and treatment are recommended for medical personnel treating a victim. As a result in the case of pesticide poisoning the label should always be taken to the emergency medical facility. On the label of Category 1 pesticide products an 800 telephone number is found that physicians may call for further treatment advice at any time. , labels for less toxic pesticides products will also provide first-aid instructions. Labels of pesticide products bearing the DANGER signal word due to skin and eye irritation potential will not carry the word POISON or the skull-and-crossbones image.

The EPA requires that “signal words” be present in most labels that are placed on pesticide products sold in the United States (U.S.).

These words describe the acute (short-term) toxicity, but NOT the potential long-term toxicity of the pesticide product. The signal word can be either: DANGER, WARNING or CAUTION.

The United States Environmental Protection agency requires signal words to occur on the front panel. These words should be in capital letters, and large enough to make it easy to see. The only pesticide products where these words are not required on a label are those that occur in the lowest toxicity category by all possible routes of exposure, namely oral, dermal, inhalation, and other effects like eye irritation. Caution on a label indicates a product is slightly toxic if consumed, absorbed via skin, inhaled, or it causes minimal eye or skin irritation. 

The WARNING on a pesticide label is an indication that the product is moderately toxic if consumed, absorbed through the skin, inhaled, or it causes moderate eye or skin irritation. 

DANGER indicates that the pesticide is highly toxic by one or more routes of exposure.  It may be corrosive, result in irreversible damage to the skin or eyes or it may be highly toxic if consumed, absorbed via skin, or inhaled. If this is the case, then the word “POISON” must also be included in red letters on the front panel of the product label. 
 

 TOXICITY CATEGORIES

Study       

DANGER Highly Toxic 

WARNING Moderately Toxic 

 CAUTION Low Toxicity

CAUTION  (Optimal) Very Low toxicity

 

Category 1  

Category 2 

Category 3 

Category 4  

Acute Oral

Up to and including 50 mg/kg

Above 50 mg/kg thru 500 mg/kg

Above 500 mg/kg thru 5000  mg/kg

Above 5000 mg/kg

Acute Inhalation *   

Up to and including 0.05 mg/liter

Above 0.05  mg/liter to and including
 .5 mg/liter

Above .5 mg/liter to and  including 2.0 mg/liter

Above 2.0 mg/liter

Acute Dermal     

Up to and including 200 mg/kg

Above 200 mg/kg and including 2000 mg/kg

Above 2000 mg/kg and including 5000 mg/kg

Above 5000 mg/kg

Primary Eye Irritation

Corrosive (irreversible damage of  ocular tissue) or corneal involvement or irritation persisting for more than 21 days

Corneal involvement or other eye irritation clearing in 8-21 days

Corneal involvement or other

eye irritation clearing in 7 days or less

Minimal effects clearing in less than 24 hours

Primary Skin Irritation

Corrosive (tissue destruction into the dermis and/or scarring)

Severe irritation at 72 hours (severe erytherna or ecema.

Moderate irritation ay 72 hours (moderate erytherna)

Mild or slight irritation at 72 hours. (no irritation or slight erytherna)

 *4 hr exposure

It should be noted that these signal words are somewhat misleading as there is quite a range of toxicity represented by each signal word. For example Pesticide A could contain a toxicant (active ingredient) that has an LD50 of 2 and Pesticide B could contain a toxicant that has an LD50 of 50. Both would have the same signal word on the label but Pesticide A would potentially be 25 time more toxic than Pesticide B, assuming both had the same amount of active ingredient and were formulated similarly. With this in mind, it is to the applicator’s advantage to know the precise LD50 of a given pesticide rather than relying on the signal words alone.

Although this does not occur on a pesticide label, the question may arise as to the acute oral lethal dose of a technical pesticide toxicant to humans. The following table illustrates the ranges of lethal human toxicities of chemicals with danger, warning and caution signal words.

Signal Words and Related Potential Dose that is Deadly.

Signal Word

Toxicity

Oral Lethal Dose Human 150 lbs

DANGER  

Highly Toxic

Few drops to teaspoon

WARNING

Moderately toxic

One teaspoon to 1 table spoon

CAUTION 

Slightly toxic

 Tablespoon to pint. 

 

PRECAUTIONARY STATEMENMTS

This section of the label includes statements indicating specific hazards, possible routes of exposure, and precautions needed to avoid human and animal injury. The label will contain statements that indicate which possible route of entry (eyes, skin mouth, lungs) that is particularly required to be protected and what specific action is needed to take to avoid acute effects from exposure to the pesticide. Examples of such statements seen in this section include: 

  • "Causes eye and skin irritation. Harmful if swallowed, inhaled, or absorbed through skin."
  • “Do not get on skin or on clothing.” 
  • “Avoid breathing vapor or spray mist.” 
  • “Avoid contact with eyes.” 
  • “Prolonged or repeated skin contact may cause allergic reactions in some individuals.” 

Products that the United States Environmental Protection Agency has determined to have the potential for a delayed reaction must have label statements warning the user of that fact. Such statements will indicate if the product has been tested to cause problems such as tumors or reproductive problems in laboratory animals. In addition, information in this section will alert users if the product has the potential to cause allergic effects, such as skin irritation or asthma. Sometimes the labeling refers to allergic effects as "sensitization."

Typical Precautionary Statements on Pesticide Labels

Exposure

Highly Toxic

Moderately Toxic

Slightly Toxic

Acute Oral

Fatal if swallowed. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet.

May be fatal if swallowed. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet.

Harmful if swallowed. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet.

Acute Inhalation

Fatal if inhaled. Do not breathe dust. Wear required respiratory protection. Remove and wash contaminated clothing before reuse.

May be fatal if inhaled. Do not breathe dusts. Wear required respiratory protection. Remove and wash contaminated clothing before reuse.

Harmful if inhaled. Avoid breathing dusts. Remove and wash contaminated clothing before reuse.

Acute dermal

Fatal if absorbed through the skin. Do not get on skin, in eyes or on clothing. Wear appropriate protective equipment and gloves. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Wear appropriated protective clothing. Remove and wash contaminated clothing before reuse.

May be fatal if absorbed through the skin. Do not get on skin or on clothing. Wear protective clothing and gloves. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove and wash contaminated clothing before reuse.

Harmful if absorbed through skin. Avoid contact with skin, in eyes or on clothing. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove and wash contaminated clothing before reuse. Wear any appropriate protective clothing, if appropriate.

 Skin Irritation

Corrosive. Causes severe skin burns. Do not get in eyes, or on skin or on clothing. Wear appropriate protective clothing and gloves. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove and wash contaminated clothing before reuse.

Causes skin irritation. Do not get on skin or on clothing. Wear appropriate protective clothing and gloves. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove and wash contaminated clothing before reuse.

Avoid contact with skin or clothing. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Wear protective clothing and gloves, if appropriate.

 Eye irritation

Corrosive. Causes irreversible eye damage. Do not get in eyes or on clothing. Wear protective eyewear such as goggles, face shields or safety glasses. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Wear appropriated protective clothing. Remove and wash contaminated clothing before reuse.

Causes substantial but temporary eye irritation. Do not get in eyes or on clothing. Wear protective eyewear such as goggles, face shields or safety glasses. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove and wash contaminated clothing before reuse.

Causes moderate eye irritation. Avoid contact with eyes or clothing. Wear protective eyewear, if appropriate. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Wear protective clothing, if appropriate..

 

PHYSICAl AND CHEMICAL HAZARDS
 
This portion of the label will indicate unique fire, explosion, or chemical hazards that are inherent to a particular product. As an example, it will alert the handler or applicator as to potential problems or even relate to how a product should be stored. If a product is especially flammable, it needs to be stored or handled away from open flames or heat. On the other hand, if a product is extremely corrosive, it must be stored in a corrosion-resistant container. This section doesn’t always occur in the same location on the labeling. On some labels these types of hazards will be discussed in a designated box. On other labels they will be found on the front panel beneath the signal word. Especially in the case of extreme characteristics they can be found under headings such as "Note" or "Important." Examples include wording such as: “Do not use or store near heat or open flame.” Some products will include statements concerning the diluted product such as: “Spray solutions of this product should be mixed, stored and applied using only stainless steel, aluminum, and fiberglass, plastic or plastic-lined steel containers.”  Many other hazards may be found in this section.

A good example of where a product has a unique characteristic is Phostoxin, Fumitoxin, or Gastoxin. These products contain aluminum phosphide. In this case there is a potential danger of explosion if handled improperly. This statement is found in the above section. Aluminum phosphide tablets, pellets, bags, and partially spent dust will release hydrogen phosphide if exposed to moisture from the air or if it comes into contact with water, acids and many other liquids. Piling of tablets, pellets, bags or dust from their fragmentation may cause a temperature increase and confine the release of gas so that ignition could occur. I used this material for years in my gopher and ground squirrel control company. I know of one company that had an explosion problem with these chemicals. The applicator’s statement was “it blew the paint off of my truck’.

A True Disaster Story
 
A friend of mine in graduate school (working towards a Ph.D in pest management) was close to completing his research. His trailer-office was located near the quite large university pesticide storage facility which contained large quantities of emusifiable concentrates. A fire started in the facility. It was huge, with 50 gallon drums exploding in the middle of the night, I could see if from half a mile away. Needless to say the trailer was also burnt to the ground. All of Ray’s research data was in there and was gone- 2 years’ worth. He had to start all over. In those days (45 years ago) we didn’t have personal computers and alternative storage sites.

ENVIRONMENTAL HAZARDS
 
This portion of the pesticide label discusses the type of potential hazards and the precautions needed to avoid injury or damage to a variety of non-target organisms and/or the environment. Certain general statements are found on almost every pesticide label. As an example, most labels will indicate to the user not to contaminate water sources when applying the product, exemplify cleaning application equipment, or disposing pesticide wastes. It is also in this section that information can be found if the product poses a threat to groundwater. Instructions will be provided to minimize such impacts. Some labels will mention endangered species concerns in this section. Warnings of potential toxicity to honeybees, fish and other animals may also be stated in this section. Examples of environmental hazard statements include: 

  • “This product is highly toxic to honeybees;” 
  • “This product is extremely toxic to fish and aquatic invertebrates;” and 
  • “Do not apply where runoff is likely to occur.”

In California, endangered species has become of special concern. The Department of Pesticide Regulation has developed an interactive mapping system (Prescribe) where an applicator can now go online to determine the possibility of the presence of a variety of endangered species and pesticide application limitation in that areas. The EPA has a similar interactive mapping system for 11 endangered species in the greater San Francisco Area. Applications and Limitations also are found in their area of habitation. See Enviromapper.

FORMULATIONS
 
The front panel of certain labels will describe pesticide formulations. The type of formulation may either be indicated by an abbreviation (e.g. .G = Granular, EC or E=emulsifiable concentrate, M=microencapsulation), WP=Wettable Powder or spelled out. There are many other types of formulations, but these are a few of the more common types. Knowing a particular type of formulation is helpful because it provides insight about the types of application equipment needed, product's handling properties and the potential hazard or advantages of a given formulation.

It is worthwhile to remember that the toxicity of the active ingredient in a product does not always correlate directly to potential hazard of that product. The hazard may vary considerably depending on the formulation of the product, concentration of the toxicant in the product, method of application and other factors. For example pesticide A when formulated as a granule presents a totally different hazard (much less) than when formulated as an emulsifiable concentrate. The granular formulation would not likely present much of a dermal hazard (as it may be coated with a nontoxic material) and the same chemical when formulated as an emulsifiable concentrate may present a high dermal hazard. These potential hazards are indicated in the precautionary statements on the labels. It is worthwhile to discuss the various types of formulation available and the potential risk from each.

A pesticide product consists of two parts, namely the active ingredient and the inert ingredient. The active ingredient is the toxicant that kills the targeted pest. The inert ingredients are solvents and carriers that help deliver the active ingredient to the pest. Inert ingredients may be liquids into which the active ingredient is dissolved, chemicals that keep the product from separating or settling, and even compounds that help secure the pesticide to its target upon application. The combination of an active ingredient with a compatible inert ingredient is referred to as a formulation.

Other factors that should be considered as to the type of a formulation to use in a given situation are discussed in a little more detail. The question may arise as to formulation choice in a sensitive area? Such areas may include food handling areas, hospitals or nursing homes, class rooms, day care location, airlines, bakeries, hospitals, certain areas at zoos and many, many more. Special precautions (including the type of formulation) must be taken in these sensitive areas to avoid potential hazards to the occupants. Of course it is extremely important to make sure a product is labeled for use in a sensitive location. Residual sprays may be limited to crack and crevice treatment and may be prohibited when rooms are occupied. Ideally, products should be selected that have low to no odor and have a low vapor pressure in these types of situations. Products that do not leave a visible residue (especially dust) may be a good idea. Certain house infesting pests (ants, cockroaches) can be controlled with baits which are an excellent choice in these types of sensitive areas.

Example

The applicators should seriously consider all potential consequences in treating a sensitive location or even possibly one that might not be totally sensitive. I have recently (in the past several years) decided to start serving as an expert witness. Needless to say, I run across situations where pesticides are used to control structural pests. A problem with that is there are lots of lawyers in California; some are great and some not so great. Here is a true situation. An applicator is brought into a given apartment unit to control for pest x. The applicator treats (fogs) following the label instructions. Several hours later the occupants returned after indicated label instructions and complained of excessive dust residue and a strong chemical odor. The occupant falls and hurts his self and claims the fall was due to a strong pesticide odor. Depending on the formulation and toxicant-this may or this may not be a problem. If the applicator used or sprayed with a wettable powder that had some odor to it, there could be a problem. However, if a fog was used containing a no odor formulation of pyrethrin (commonly fogged), there would be no validity to such a claim. First of all such a formulation would leave no visible residue and, secondly, there would be no problem with odor. Fortunately Pyrocide contains pyrethrum and based on the history of this chemical, relative low toxicity and the fact that it does not leave a residue (liquid ULV Formulation) and is low odor. Because this was a lawsuit, I was called to verify this fact even though the label would back my conclusions. Fortunately the owner of the complex had an open unit of the same size. I had the applicator spray this unit using the exact same procedure. Prior to application I placed 4 large ceramic tiles in the unit. One half hour after spraying I entered the unit and there was no odor. I also removed the sprayed tiles and 2 to 4 hours later I had 6 different individuals attempt to determine (via smell, sight) if they could determine (choose) an unsprayed tile that was compared to the 4 sprayed tiles. None of these individuals could correctly make that determination.

Solid Formulations

Solid formulations can be divided into two types: ready-to-use, and concentrates which must be mixed with water to be applied as a spray. Three of the solid formulations (dusts, granules, and pellets) are ready-to-use, and three (wettable powders, dry flowables, and soluble powders) are intended to be mixed with water.

Dusts

Dusts formulations are produced via the sorption of an active ingredient (a.i.) onto a tiny/ground, inert solid such as talc, chalk, ground walnut shells, or clay. They are typically simple to use requiring no mixing and application equipment (e.g., hand bellows and bulb dusters) is lightweight and simple. Dusts will typically provide excellent coverage, but due to the small particle size creates a potential inhalation and drift hazard. In general, these types of formulations are no longer used in large scale outdoors. Structural pest control applicators use dusts effectively in residential and institutional settings for control of cockroaches, silverfish, bedbugs and many other pests. Indoors, this type of formulation permits the delivery of an insecticide into cracks and crevices, behind baseboards, cabinets, and into walls. Thus, the insecticide is placed into the pest’s habitat and away from contact by people and pets.

Granules

These types of formulations are similar to dusts, but their particles are larger and heavier. These components consist of materials such as clay, corncobs, or walnut shells. The toxicant either coats the outside of the granules or is absorbed into them. The percentage of active ingredient is typically low, usually ranging from 1 to 15% by weight. Granular pesticides are most commonly used for soil application for the control of weeds, nematodes, and soil dwelling arthropods, or as systemic through plant roots. Granules are occasionally applied by air to minimize drift or due to their heavier weight to penetrate dense vegetation. 

Once applied, granules release the active ingredient slowly. Some granules require soil moisture to release the active ingredient. Granular formulations also are used to control larval mosquitoes and other aquatic pests. Granules are used in agricultural, structural, ornamental, turf, aquatic, right-of-way, and public health (biting insect) pest-control operations. There is also a reduced inhalation hazard (compared to dusts), but finer particles are frequently associated with the formulation – especially when a bag is being emptied. In addition granules have a low dermal hazard, especially those that are coated with nontoxic materials. 

Pellets

Pellets are quite similar to granules, but they are produced differently. The toxicant is added to inert materials to form a slurry, a thick liquid mixture. This slurry is subsequently extruded under pressure through a die and then cut at needed lengths to produce a particle or pellet that is quite uniform in size and shape. These types of formulations are commonly used for spot applications. As might be expected, the use of these formulations provides high degree of safety to the applicator. They do have the potential to roll on steep or frozen slopes and thereby harm non-target vegetation or contaminate surface water.

Wettable Powders

Wettable powders are dry, finely ground formulations that appear as dusts. They normally are mixed with water and applied as a spray. Wettable powders contain 5 to 95 % active ingredient and typically 50 % or more.

To prepare a spray suspension, you must form a slury. Mix a wettable powder WP with a small amount of water, and then dilute this slury mixture further. Wettable powders are effective for most pest problems and in most types of spray equipment where agitation is possible. They have excellent residual activity and do not usually harm treated surfaces. When you apply a WP spray suspension to a target, most of the pesticide remains on the surface. This is true even for porous materials, such as concrete, plaster, and untreated wood. In such cases, only the water carrier penetrates the porous material. Wettable powder particles remain on the treated surface and thus are effective on any pest coming in contact with that surface. The particles do not dissolve but suspend in water. They readily settle out constantly require agitation to keep them suspended.

Advantages. These formulations are easy to store, transport, measure and mix. These have a bonus when compared to emusfiable concentrates and similar petroleum-based products in that there is much less of a chance of causing phytotoxicity in treated plants, harming animals, and damaging susceptible surfaces. Absorption through the skin and eyes is much less likely than emulsifiable concentrates and other liquid formulations.

Disadvantages. Since most of these products contain a high percentage of active ingredients and are basically a dust, there is a high inhalation hazard to applicator when measuring and mixing the concentrated powder. Wettable powders require vigorous and continuous agitation (typically mechanical) in the spray tank and will readily settle out once the agitator is turned off. Due to their solid component wettable powders are abrasive to many types of pumps and nozzles and hard to mix in very hard, alkaline water.

Dry Flowables

Dry flowables or water dispersible granules are  produced in the same manner as wettable powders formulation except that the powders are aggregated into granular particles. They are mixed with water and applied in a spray like wettable powders. An advantage compared to wettable powders is in the mixing and loading process. These formulations pour more easily from the container than wettable powders and because of their larger particle size, reduce inhalation hazard to the applicator.

Soluble Powders

Soluble powders, although not particularly common, are worth mentioning for purposes of contrast with the wettable powders and dry flowerless. Their lack of availability is due to the fact that not many solid active ingredients are soluble in water. Those that do exist and are formulated in this fashion are mixed with water prior to spraying, dissolve in the spray tank, and form a true solution. Soluble powders, like any finely divided particle, can present an inhalation hazard to applicators during mixing and loading.

Liquid Formulations

Liquid Flowables
 
The manufacture of liquid flowables (or flowables) mirrors that of wettable powders—with the additional step of mixing the powder, dispersing agents, wetting agents, etc., with water before packaging. The result is a suspension that is further diluted with water before use. The product is applied as a spray with all the advantages of a wettable powder. The benefit of this formulation is that there is no inhalation hazard to the applicator during mixing and loading since the powder already is suspended in water, permitting it to be poured. One potential problem noted with this formulation is the difficulty in removing the entire product from the container during mixing, loading, and container rinsing.

Microencapsulated Formulations

Pesticides can be microencapsulated by suspending the pesticide particle or droplets in plastic polymer of various types. By altering the chemistry of the polymer or changing factors in the processing, microcapsules can be formed of various sizes, solubilities, wall thickness and degree of penetration. These factors affect the residual activity, speed of performance, odor and safety of the product. The microcapsules are suspended in a liquid base so that the final formulation is a flowable suspension. The formulation is then mixed with water and requires regular agitation to prevent capsules from settling out. These types of formulations are mixed with water and sprayed in the same manner as other sprayable formulations. Subsequent to application the tiny capsules begin to break down and slowly release the toxicant.

These formulations have several advantages. Because the toxicant is initially contained in a microcapsule the formulation is safer for applicators to mix and apply. The oral toxicity of many of the capsules is greatly reduced to non-target animals, including humans. In many cases the microcapsules can pass though the human digestive tract without releasing significant amounts of the toxicant. Because the toxicant is gradually released from capsule the effectiveness of an application is prolonged thus increasing its residual activity. These formulations often reduce or minimize phytotoxicity. In addition microcapsulated formulations perform well on both porous and non-porous surfaces and typically have little or no odor.

Volume Formulations
 

These are used in the structural industry in the form of misting with aerosol generators. In this case pyrethrins are used in aerosol generators to produce very fine mists. Prior to this longer residuals may be applied in those locations where the roaches are normally found. Pyrethrin when used in an aerosol generator is not generally considered an excellent way to control German cockroaches since it is a “weak” pesticide and as an aerosol does not penetrate in a high enough concentration to kill the roaches but it does agitate the vermin and drives them out of hiding and thus contacting the already applied residual pesticide.

Emulsifiable Concentrates

Emulsifiable concentrates consist of an oil-soluble active ingredient dissolved in an appropriate oil-based solvent to which is added an emulsifying agent. Emulsifiable concentrates are mixed with water and applied as a spray. As their name implies, they form an emulsion in the spray tank. The emulsifying agents are long chain chemicals that orient themselves around the droplets of oil and bind the oil-water surfaces together to prevent the oil and water from separating. Emulsifiable concentrates allow oil-soluble active ingredients to be sprayed in water as a carrier. Since these types of formulations have a high active ingredient (toxicant) concentration, it easy to overdose or under-dose when mixing or calibrating. Of course under-dosing may lead to reduced control on targeted pest while overdosing may lead to excessive residues on the crop and above pesticide tolerance levels at the time the crop goes to market. Depending on the solvent used and crop treated phytotoxicity may be a problem. Emusifiable concentrates are readily absorbed through skin: plus their high percentage of toxicant prior to mixing typically necessitates the use of protective equipment during mixing and loading. The solvents in emusifiable concentrates may lead to rubber or plastic hoses, gaskets, and pump parts to break down over time. In addition these formulations are capable of pitting or discoloration of painted finishes. Ultimately emusifiable concentrates are flammable—should be used and stored away from open flames or excessive heat. Some products may have a strong odor. Splashes and spills are relatively difficult to clean up and/or decontaminate.

Solutions. (water-soluble concentrates). These consist of water-soluble active ingredients dissolved in water for sale to the applicator for further dilution prior to field application. They will, obviously, form a true solution in the spray tank and require no agitation after they are thoroughly dissolved. Although not a particularly common formulation, several major herbicides with wide-scale use are formulated in this way. They include products containing paraquat, glyphosate and 2,4-D. Aside from lack of availability, solutions have few disadvantages; however, some that are produced as dissolved salts can be caustic to human skin.

PERSONAL PERSONAL PROTECTIVE EQUIPMENT

The majority of pesticide labels list specific instructions relating the type of clothing that must be worn while handling and mixing products. These instructions are typically located following the statements regarding acute, delayed, and allergic effects. This information can also be found on the label after the signal word. A few examples of many statements from pesticide labels regarding personal protective equipment include:

  • “chemical-resistant footwear plus socks;” 
  • “long-sleeved shirt and long pants;”
  • “waterproof gloves;” 
  • “protective eyewear” and many other similar statements. 

The type of equipment that is listed is the minimum protection that must be worn while handling the pesticide. Sometimes this information will require different personal protective equipment for different pesticide activities. Typically greater safety equipment is required when performing pesticide operations that involve handling concentrated products. In some cases, reduced personal protective equipment is allowed when you will be applying the pesticide in safer situations, such as enclosed cabs. 

There are strict laws, both federal and state (DPR) that indicates the type of protective equipment that is required when handling pesticides. The pesticide label of a given product will indicate the type of personal protection required. California requirements for use of personal protective equipment in some cases are more restrictive than those provided by the EPA.

Gloves
 

Materials used to make gloves for pesticide use include natural rubber (latex), polyethylene, nitrile, butyl, neoprene, polyvinylchloride (PVC) and barrier laminates like 4H® and Silver Shield®. The most recent information on the protectiveness of these materials indicate that nitrile, butyl, and neoprene give good protection for both dry and liquid pesticides but neoprene is not recommended when applying fumigants. Natural rubber is the least effective of these materials when working with most products and formulations, and is only effective for dry formulations. Leather or cotton gloves should not be used. Leather and cotton gloves can be more hazardous than using no protection at all simply because they easily absorb pesticides and as a result hold them close to the skin for extended periods of time. It is important to examine the quality and type of material used prior to purchasing any glove due to the fact that efficacy varies from manufacturer to manufacturer. Generally speaking protection increases with the thickness of the materials, but extra thick gloves may interfere with dexterity. In no case should fingerless gloves be used when working with pesticides.

It is always advisable to closely check for holes via filling the gloves with air or clean water and gently squeezing. If any holes are found the gloves should be discarded. When applying chemicals overhead, the cuffs should form a cup to catch any liquid that could runs down the arm. Once finished spraying, gloves should be thoroughly washed with detergent and water prior to removing to avoid contaminating the hands or the inside of the gloves when in the process of removing. The applicator’s hands should be washed with lots of soap once the gloves are removed.

Clothing
 
The use of normal work attire consisting of long pants and a long-sleeved shirt, shoes, and socks are acceptable when using slightly toxic (category III) and relatively non-toxic (category IV) pesticides. Many applicators prefer work uniforms and cotton coveralls. Regulations in California require the use of coveralls for pesticides labeled Warning and Danger. Regardless of which type of clothing used, one set of clothing should be used for pesticide work with no other use. These materials should be laundered and stored separately from all other clothing.

Protective suits that are clean and dry and cover the entire body, including ankles and wrists, are a must when applying moderately toxic (category II) or highly toxic (category I) pesticides. The sleeves must reach past or overlap with gloves. Protective clothing should be worn over regular work clothes and underwear and is commercially available as disposable or reusable models. They are commercially available in woven, nonwoven, coated and laminated fabrics. The degree of protection increases from woven to nonwoven to coated and laminated fabrics. The pesticide label will indicate the type of suit should be used when working with various types of pesticides. Uncoated nonwoven fabrics are convenient for use when working with product formulated as dust, granule, or powder. On the other hand, they will not provide adequate protection against spills, sprays, or mists and are not recommended for use with liquid pesticides. Fabrics are more resistant to pesticide penetration with laminating fabric layers and/or by applying chemical coatings. Chemical -resistant protective suits of coated or laminated fabrics are a must when mists or spray wet clothing. Coated and laminated fabrics resist water penetration, but not all of these are chemical resistant. Chemical-resistant suits are recommended when handling highly toxic (category I) pesticides.

Boots 

When required by the label the applicator or mixer loader should wear unlined chemical-resistant boots which cover his or her ankles when handling or applying moderately or highly toxic pesticides. Ideally these boots should have thick soles. Nitrile and butyl boots appear to provide the best protection. In no case should these individuals use leather boots. If chemical-resistant boots are too hot in warm climates or too difficult to put on, chemical-resistant over-boots with washable shoes (such as canvas sneakers or layered socks) are a viable alternative. Pant legs should be outside the boots, otherwise the pesticide can drain into the boot. These boots should be washed after each use and dried thoroughly to remove all pesticide residues.

Goggles/Face Shields

Wear either shielded safety glasses, snug-fitting non-fogging goggles, or a full-face shield in situations where these chemicals have any possibility of contact to your eyes. Safety glasses with brow and fitted side shields are permitted in low exposure applications. However, goggles or full-face respirator are a must when pesticide handlers are pouring or mixing concentrates or working in a highly toxic spray or dust. In high exposure situations when both face and eye protection are needed, a face shield can be worn over goggles. 

Part II: Pesticide Classification, Poisoning, Safety

MEASURING TOXICITY

The toxicity of a pesticide is determined by laboratory testing on animals such as rats, mice and rabbits. The measuring method, LD50 (lethal dose, 50 percent), describes the dose of a pesticide that will kill half of a group of test animals from a single exposure (dose) by either the dermal, oral or inhalation routes. A pesticide with a lower LD50 is more toxic than a pesticide with a higher number because it takes less of the pesticide to kill half of the test animals. The toxicity of fumigant pesticides is described in terms of the concentration of the pesticide in the air, LC50 (lethal concentration, 50 percent). A similar system is used to test the potential effects of pesticides against aquatic organisms in water.                                             

Two additional terms are commonly used when measuring pesticide toxicity, namely acute and chronic toxicity. Acute toxicity occurs from one exposure or multiple exposures over a short time. This type of toxicity is commonly used in combination with the previously described terms. For example, if a given pesticide had an LD50 of 20 it would require a dose of 20 milligrams (per kilogram of body weight) to kill 50% of a test animal population when administered via one dose through the mouth.

Chronic toxicity is the effects of lengthy or repeated lower level exposures to a toxicant. These effects do not appear immediately after an initial exposure and may take a year or more to produce signs and symptoms. Examples of this type of poisoning may include: Carcinogenicity - exposure may result in cancer; mutagenicity - exposure may result in genetic changes;  teratogenicity - exposure may result in birth defects; oncogenicity - exposure may result in the development of tumors  (not necessarily cancers); liver damage - exposure may result in destruction of liver cells,  jaundice (yellowing of the skin), fibrosis and cirrhosis; reproductive disorders - exposure may result in or produce reduced sperm count, sterility, and miscarriage; nerve damage - including accumulative effects on cholinesterase depression associated with organophosphate insecticides; allergenic sensitization - development of allergies to pesticides or chemicals used in formulating pesticides. 

The symptoms of chronic toxicity, as with acute toxicity, are dose-related. Put more simply, low-level exposure to pesticides that exhibit a potential to cause long-term symptoms but may not result in immediate injury. On the other hand, repeated exposures can greatly increase the risk of chronic adverse effects.

REPORTING PESTICIDE POISONING

It is estimated that annually in the U.S there are between 10,000 to 20,000 cases of work-related pesticide poisonings. A quick survey of Table 1 reveals that two thirds of these poisonings occur in children under the age of six. These data do not reflect suicide/homicide cases and focus on symptom producing poisonings.

In about 90 percent of pesticide poisoning cases, only minor symptoms occur and are typically treated at home. However, the chemicals in 5 of the top 8 listed categories (carbamates, organophosphates, pyrethrin/pyrethroids, organochlorines, and anticoagulant rodenticides) are much more likely to require medical attention. It should be noted that this table is not representative of all pesticide poisonings as it only reflects those cases reported to the National Poison Control Center. The actual number of poisonings is likely much higher. It should also be noted that these data are somewhat old and the use of the organophosphorus and carbamate insecticides has been greater curtailed in the past few years: however, it is still significant that many of those that are still in use are relatively more hazardous than most chemicals in the other categories.

Pesticides most often implicated in symptomatic illnesses, 1996.

Rank

Pesticide or pesticide class

Number of cases

 

 

Children less than 6 years old

Adults and older  children

Total

1

Organophosphates

700

3,274

4,002

2

Pyrethrins and pyrethroids

1,100

2,850

3,950

3

Insect repellents

1,081

997

2,086

4

Carbamates

202

817

1,030

5

Organochlorines

229

454

685

6

Phenoxy herbicides

63

387

453

7                 

Anticoagulant rodenticides

176

 33

209

8

All other pesticides

954

3604

4623

Findings based on data from The American Association of Poison Control Center

  Pesticides most often implicated in acute occupational pesticide-related illness and injury and number of cases — SENSOR-Pesticides program, United States, 2007–2010 

Pesticide category

Pesticide
functional class

Exposed to single
substance*

Exposed to multiple substances†

All cases (single and
multiple exposure)†

 

 

No.

(%)

No.

(%)

No.

(%)

Pyrethroids

Insecticide

244

(59)

172

(41)

416

(21)

Organophosphorus compounds

Insecticide

160

(59)

111

(41)

271

(13)

Glyphosate

Herbicide

105

(64)

58

(36)

163

(8)

Pyrethrins

Insecticide

68

(49)

71

(51)

139

(7)

Sulfur compounds

Insecticide/Fungicide

66

(50)

65

(50)

131

(7)

Organochlorine compounds

Insecticide

12

(17)

60

(83)

72

(4)

N-methyl carbamates

Insecticide

42

(72)

16

(28)

58

(3)

Phosphorus

Fumigant

52

(95)

3

(5)

55

(3)

Dipyridyls

Herbicide

28

(52)

26

(48)

54

(3)

Thiocarbamates/Dithiocarbamates

Fumigant

41

(79)

11

(21)

52

(3)

Pyraclostrobin

Fungicide

32

(74)

11

(26)

43

(2)

Chloropicrin

Fumigant

3

(8)

35

(92)

38

(2)

Fipronil

Insecticide

5

(14)

30

(86)

35

(2)

Imidacloprid

Insecticide

1

(3)

28

(97)

29

(1)

Triazines

Herbicide

12

(50)

12

(50)

24

(1)

All other

419

(52)

392

(48)

811

(40)

Total

1,290

(64)

724

(36)

2,014

(100)

Abbreviation: SENSOR = Sentinel Event Notification System for Occupational Risks

 A pesticidal active ingredient.

† Because some persons who were exposed to multiple substances appear in the totals of more than one pesticide category, the sum of the pesticide categories in this column exceeds the number of individual persons.

It is of interest to note that based on a comparison of the two tables above, which are based on information up to 12 years apart, that in the first table the organophosphorus insecticides rank highest on the number of record cases of pesticide poisoning while pyrethroids are ranked highest in the second table. This is not surprising due the current popularity of the pyrethroid chemicals used in agriculture, the structural pest control industry and even home use. Even though most of these have been phased out for use, the organophosphorus insecticides rank second in the most recent table. This possibly relates the more “toxic” nature of some of these chemicals. Of interest are the glycophosphate herbicides in the second table are ranked third. Technically glyphosate is relatively low toxicity, but these products commonly possess other ingredients that help the product get into the plants. The other ingredients found in pesticides can make a given product more toxic. Pesticides containing the toxicant glyphosate may result in eye or skin irritation. Individuals who breathe in spray mist from products containing toxicant resulted irritation in their nose and throat. Most significantly the tables reflect a decrease in the number of poisoning over the years which undoubtedly reflects in the use of less toxic pesticides and the increase in pesticide safety laws and regulation both at the state and federals level.

ROUTS OF ENTRY INTO BODY

A major factor that greatly influences the risk of a pesticide product is its route of entry into the body. Pesticides can enter the human body a number of ways, including through the skin (dermal), the eyes (conjunctival), the mouth (oral), and by breathing (inhalation).

Dermal/Conjunctive Exposure

Pesticides can easily enter through the skin and eyes. Entry through the eye is generally the most rapid means, with other dermal entry rates varying quite drastically, depending on the particular area of the skin.

The relative rate of absorption of pesticides through the skin over various areas of the body, compared
to the rate tested on the forearm.

The relative rates of pesticides absorption through the skin are calculated by comparing them to the rate tested on the forearm. As an example, a pesticide can enter the body 4.2 times faster through the forehead than through the forearm. Pesticides can absorbed faster through the skin on the head (forehead, ear canal skin, and scalp) and groin than through the skin on the forearms, balls of the feet and palms. This is significant as pesticide residues can be easily transferred from one area to another area of the body. If this happens, the operator will increase the potential for poisoning of pesticides moved from a hand to a sweaty forehead or to the genital area. At the very highest rate (groin), the absorption of a pesticide through the skin may be more dangerous than if swallowed! 

Oral Exposure
 

Generally speaking, pesticides are absorbed more rapidly when ingested than when exposed to most areas of the skin and when ingested can result in serious injury or death. This is even true for some of the “relatively nontoxic pesticides”. In some cases the solvents used in formulating a product are more toxic than the so-called toxicants. The most common type of oral exposures is the result of when products are removed from one original container into a soft drink bottle or some other type of food container. Children 10 or under are victims of at least 1/2 of the accidental pesticide poisoning deaths in the United States. It is considered a serious violation to store a pesticide in a food or similar container.

Respiratory Exposure

Inhalation of pesticide particles is especially hazardous as they are rapidly absorbed by the lungs into the bloodstream. Besides acute or chronic pesticide poisoning, these products can cause considerable damage to lungs, the nose, and throat. Vapors and small particles present the most serious risks. When using low-pressure application equipment, the majority of sprayed droplets are considered too big to remain suspended in the air long enough to be inhaled. On the other hand, if high pressure, ULV, or fogging/misting equipment is used, the potential for respiratory exposure is increased considerably. The droplets produced during these operations are relatively small and can be carried on air currents for considerable distances.

FOOD SAFETY AND PESTICIDE RESIDUE

The product that is applied on the leaves, fruit, other agricultural products or any other surface immediately after application is considered a deposit. If this so called deposit stays on the given surface for a given period of time, it is then a residue. Some pesticide products leave little or almost no residue. Most importantly various environmental conditions such as heat, light, microorganisms, soil chemistry, salinity, moisture, soil organisms, and other chemical reactions break these toxicants down to nontoxic byproducts over time. Depending on the product and existing environmental conditions, this residue may remain on a surface or in the environment for hours, days, weeks, months, or more. Each pesticide varies in how long its residue remains on the crop or surface. Therefore, information on residues is required on each crop the pesticide is applied to.

Pesticides On or In Food and Tolerances

A massive quantity of information is gathered and studied before tolerances (permissible amount of pesticide on a food item) are established on a given product. Prior to registration of a pesticide federal and state agencies (DPR, EPA) require extensive toxicity testing on a number of vertebrate and invertebrate animals in order to determine the acute and chronic toxicity of the chemical. Toxicity to fish, birds, rodents and other mammals, the residual activity of the product in the environment, possible long-term effects such as bioaccumulation in animals or in the environment are thoroughly tested and evaluated. All these factors (and others) are thoroughly studied and evaluated prior to setting pesticide tolerances. Generally these tolerances on agricultural produce are typically set at least 100 times less than the maximum dose that had a no observable effect level (NOEL) in test animals. As an example, if 200 (per per million) of pesticide toxicant had no observable effect level on test animals, then the tolerance for that given pesticide any food or feed crop could be no higher than 2 parts per million (ppm) at the time it goes to market. As a result there has been created a “safety factor" of 100 times. Products that are part of the normal diet of babies or young children are of special concern when setting these tolerances on food. Federal law requires that a tolerance be set for every food or feed use of each pesticide before it is registered in California and the United states. The tolerances vary from crop to crop depending on the many safety factors involved. If a residue is found that exceed the established tolerance of a given pesticide on a given crop (food) at the time it goes to market, the commodity will be subject to seizure.                                                 

CLASSIFICATION OF PESTICIDES

Pesticides may be classified by several ways. One traditional means places them in one of two groups, namely organic and inorganic. Organic pesticides, simply put have carbon as the basis of their molecular structure. These chemicals that are organically based are more complex and usually do not readily dissolve in water. As indicated inorganic pesticides are simpler compounds. They are environmentally stable meaning they tend to persist in the environment, and typically dissolve readily in water. The earliest chemical pesticides were inorganic, and included substance such as sulfur and lime. The majority of insecticide in this group has fallen way to newer chemicals. Almost all modern pesticides are organic in nature. Besides having a carbon molecule in their structure, there are currently untold numbers pesticides developed based on organic chemicals, often with oxygen, phosphorus, or sulfur in their molecules. Organic pesticides are subdivided into two groups: namely natural organics, and synthetic organics. The natural organic pesticides or just "organics’ ‘as their name implies’ are mostly extracted from naturally occurring sources such as plants. Rotenone and pyrethrum are examples of natural organic pesticides. Synthetic organic pesticides are, as their name implies, synthetically produced. This group comprises the so called "modern" pesticides and were discovered and began their post-World War II use, and includes DDT, permethrin, Malathion, 2, 4-D, glyphosphate, and many, many others.

Inorganic Insecticides

There are basically two different types of inorganic pesticides used today, namely borates and silica based compounds. Each has a different mode of action. Boric acid is mainly formulated as a powder or bait either of which must be ingested to be effective. As a dust it is ingested via the insects grooming activity. Of course baits are consumed orally. The mode of action of borates is not well understood but they possibly interfere with an insect’s metabolism at a cellular level and are used for the control of cockroaches, ants and other insects inside structures. Because it is used in residences, boric acid powders do present a hazard to children. It is moderately irritating to skin and if inhaled causes irritation of the respiratory tract and shortness of breath. In severe cases where babies are heavily exposed, a beefy red skin rash, most often affecting palms, soles, buttocks, and scrotum, has been described. 

Silica base compounds work by either absorbing the waxy layer on the outside of the insect’s exoskeleton or abrading the waxy layer. Water loss is a big problem with insects. Because insects are small, they have a large surface area in relation to their total body volume to store water. This outer waxy layer on the outside of an insect’s exoskeleton functions to minimize water loss from the insect’s body. As a result, if it removed via absorption (diatomaceous earth base products) or abraded off (silica based pesticides) the affected insect soon dries up and dies. Silica gels pesticides are typically considered more effective than diatomaceous earth pesticides.

Botanic Pesticides

The toxicants or active ingredients in products come from variety of sources with a few extracted from plant parts and are referred as the botanicals. These include rotenone, nicotine, and pyrethrum. A few have mineral origin or are based on microbes, the most common of which is Bacillus thuringiensis. However, the overwhelming vast majority of these are synthetically produced in the laboratory

Bacillus thurengensis (Bt) is a bacterium that naturally occurs in soil. It produces spores and crystalline proteins that have been used to control insect pests since the 1920s. There are different forms of this bacterium that are currently used as specific insecticides. These are available in a variety of trade names such as ThuricideBerliner (B.t. variety kurstaki): Dipel, Thuricide, Bactospeine, Leptox, Novabac, Victory, Certan (B.t. variety aizawa). Teknar (B.t. variety israelensis).

This insecticide was originally registered by the Environmental Protection Agency in 1961 as a general use insecticide. A registration standard, issued in 1986 by the EPA, required developers to make minor changes in label precautions and to provide supplemental data on the effects of this chemical on nontarget organisms. Even though the United States Environmental Protection agency considers the toxicological data base for B.t. complete, they still may require more ecological effects data.

Bacillus thurengensis is generally considered ideal for pest management and organic gardening as a result of the fact that it is specific to pests it will kill and the inherent lack of toxicity to humans or the biological control insects and mites of a significant number of crop pests. There are currently several different strains of this bacterium and as indicated these produce specific toxicities to particular types of insects: B.t. aizawai (B.t.a.) is used to control wax moth larvae that attack combed wax; B.t. israelensis (B.t.i.) is effective on the larvae of a number aquatic insect such as mosquitoes, blackflies and some midges; B.t. kurstaki (B.t.k.) targets various caterpillars such as the gypsy moth and cabbage looper. A newer strain of this bacteria B.t. san diego, has been found to be effective against certain beetles -most importantly the boll weevil. 

This bacterium produces spores which functions as a survival mechanism in adverse environmental conditions. During the process of spore formation, Bacillus thurengensis simultaneous produces unique crystalline bodies. It is these spores and crystalline bodies which when consumed are toxic to a variety of insects, depending on the strain of the bacterium. These crystals dissolve in response to intestinal conditions of susceptible insect larvae. This in turn paralyzes the cells in the gut, thus interfering with functional digestion and triggers the insect to cease feeding. The spores subsequently invade other pest tissues. They multiply in the insect's blood until the insect dies.

Avermectins

The avermectins are compounds that occur in the soil bacterium Streptomyces avermitilis. On the other hand, Abamectin is a natural fermentation byproduct of this bacterium that has found to have insecticidal properties. It is used to control insects and mite pests of a variety of agricultural and ornamental crops. Ivermectin, a similar member of the avermectin family of compounds, is commonly used by the World Health Organization to treat onchocerciasis (river blindness). Abamectin is a highly toxic material, however most formulated products contain low quantities of this active ingredient and are of low toxicity to mammals. Emulsifiable concentrate formulations may cause moderate eye irritation and mild skin irritation. Symptoms of poisoning observed in laboratory animals include pupil dilation, vomiting, convulsions and/or tremors, and coma.

The mode of action of this toxicant in insects is interfering with neural and neuromuscular transmission. It affects a type of synapse located only in the brain which is normally protected by the blood-brain barrier. However, at extremely high doses, the mammalian blood-brain barrier is penetrated resulting central nervous symptom depression such as in coordination, tremors, lethargy, excitation and pupil dilation. Very high doses have caused death from respiratory failure.

SYNTHETIC INSECTICIDES CLASSIFICATIONS AND MODE OF ACTIONS

As their name implies, these pesticide do not occur naturally and are synthetically produced by various chemical processes in the laboratory. There are many different classifications of insecticides and each with various different modes of actions. A mode of action is either a functional or anatomical change at the cellular level in a living organism after exposure of a substance. Common insecticide classifications are:

SYNTHETIC TYPES

·      Insect Growth Regulators

·      Organophosphates

·      Carbamates

·      Neonicotinoids

·      Pyrethroids

Insect growth regulators, or IGRs. These are synthetically produced hormone mimics. IGRs prevent insects from reaching productive age by inhibiting essential hormones. IGRs can be divided into two groups: hormonal regulators that disrupt metamorphosis and disruptors of chitin synthesis. IGRs do not kill adult insects.

It is worthwhile to discuss the function of hormones in the molting and growth process in insects. There are 3 primary hormones involved in this process, namely the brain hormone, the juvenile hormone or JH and the molting hormone or ecdysone. The brain hormone is produced by a small gland at the base of an insect’s brain. This hormone is secreted in the insect’s blood and carried to a gland in the prothorax of immature insects (larvae, grub, maggot, etc.). The function of the brain hormone is to stimulate the prothoracic gland to secrete a second hormone or ecdysone. The final hormone or juvenile hormone is produced by another gland in the brain and functions to determine what an insect molts into. Ecdysone controls when molting occurs and the rate of cell proliferation or growth. If there is a high level of juvenile hormone in the blood (in relation to the level of ecdysone in the blood) the insect will stay in a juvenile state (larva to larva, nymph to nymph). If there is a low level of juvenile hormone in the blood during molting, the immature insect will molt into an advanced stage.

Scientists have chemically identified some of these hormones with the idea of using them for pest control. They have not attempted to identify the brain hormone as the molecule is too complicated and once identified would be difficult to synthesize. They initially stayed away from ecdysone as it contains a steroid component. Since humans also have steroids in their bodies, the scientists were afraid such a chemical might have a difficult time passing the EPA registration process. As a consequence the juvenile hormone molecular structure was identified. However, since a naturally occurring chemical cannot be patented, the molecular structure of the juvenile hormone was not used in develop a pesticide. Instead the scientists slightly changed the molecular structure and slapped a wide patent on it, hence the name juvenile hormone mimics.

Juvenile hormone (JH) mimics are not quite as active in their effects as the natural hormone. However, if levels of JH mimics remain high, the insect does not advance in stage. If you prevent the insect from becoming adults, there can be no reproduction. After exposure to JH, insect death typically occurs when insects molt from the last instar to the adult. Other potential effects of these mimics on insects include: sterilization of adults, inhibition of egg hatching and deposition of nonviable eggs. Early JH products such as hydroprene and methoprene did not have very good stability when used in outdoor settings and exposed to sunlight. As a result uses were confined primarily to indoor control of roaches, fleas and stored product pests. But methoprene administered to cattle—once it has passed through the digestive system—affects maggots present in the cattle dung. More recently developed products containing fenoxycarb and pyriproxyfen have good stability and are used in exterior applications.

Metamorphosis disruptors mimic the insect molting hormone ecdysone which disrupts molting, metamorphosis and the reproductive system of female insects. Immature insects that are exposed to the ecdysone mimics typically molt prematurely or die before they can complete a molting. Any juvenile insect that is able to molt after exposure typically result in a deformed adult individual which cannot properly feed, disperse or reproduce.

An insect’s exoskeleton is largely composed of chitin which gives it strength. Therefore disruptors of chitin synthesis often results in insects with weak exoskeletons. Juvenile insects exposed to a chitin inhibitor will continuing to grow normally until they molt. The chitin inhibitor will prevent the new exoskeleton from forming after molting resulting in death. These types of inhibitors are often use in the control of termites and fleas.

Common examples of IGRs are:

  • Azadirachtin
  • Hydroprene (Gentrol)
  • Methoprene (Precor)
  • Pyriproxyfen (Nyguard, Nylar, Sumilarv)
  • Triflumuron (Starycide)

Mode of Action: Nervous system

A number of pesticides’ modes of action affect the nervous system of the target pest. To better understand how these insecticides work it is important to have a brief overview on the workings of nerves and how they communicate. 

Nerve cells do not touch. Instead there is a small space between one nerve cell and another called the synapse. It is in this space that chemical information is transferred from one nerve cell to the other nerve cell. This chemical information is picked up by a nerve cell by receptors that are found on the nerve cell axon surface. It is this chemical information pathway that many nerve poisons target by either interrupting or stimulating messages between synapses and axons. There are two chemical channels within nerves that induce or disrupt nerve activity: sodium and chloride. Sodium stimulates nerve activity while chloride inhibits nerve activity. 

Organochlorines Mode of Action: Nervous system - Sodium channels

Organochlorines function on insect nerve cells by opening the sodium channels which causes the neurons to fire spontaneously. This leads to spasms within the insect and eventually death. Some of the first chemicals synthesized for use as a pesticide are the organochlorines, the most well-known of which is dichlorodiphenyltrichloroethane, or DDT. Swiss scientist Paul Müller created DDT and for that was awarded the Nobel Prize, in the category of “Physiology or Medicine,”  in 1948. 

DDT was heavily used in the 1940s and 1950s, particularly during World War II to control vector insects of typhus, nearly eliminating the disease in Europe. DDT was also used during this time for the control of malaria and dengue in the South Pacific. DDT also played an important role in the elimination of malaria from North America and Europe. 

The use of DDT was made available to growers in 1945 as an agricultural insecticide. However, in the 1940s scientists began to worry about the potential hazards of DDT and regulations began to be put in place to govern its use. Rachel Carson, a naturalist author, after learning about concerns wrote about the use of pesticides and their potential effect on the environment in here best-selling book, Silent Spring. This book became known nationally and President John F. Kennedy tasked the Science Advisory Committee on investigating the validity of Carson’s claims. Finding much evidence to support her thesis the Science Advisory Committee suggested a phase out of “persistent toxic pesticides”. During this time DDT came under scrutiny and evidence found that DDT is a persistent organic pollutant. As DDT is readily absorbed into soils it can persist for many years in the environment. There are also issues of bioaccumulation, especially in predatory birds, which is then stored in an animal’s body fat. DDT is toxic to many non-target animals, including crayfish, daphnids, sea shrimp and many fish. In addition it causes thinning in eggshells, which results in egg breakages and embryo death. Due to these issues, by 1973 the use of DDT was banned within the United States by the Environmental Protection Agency.

Organophosphates. Mode of Action: Nervous system – acetylcholinesterase inhibition

Due to their less persistent nature, the organophosphates soon replace the organochlorides. The organophosphates degrade quickly via hydrolysis after exposure to air, soil, and sunlight. 

Mechanism of Cholinesterase Inhibition and Subsequent Poisoning in Humans:

 Part of the human nervous system is composed of thousands and thousands of nerve fibers, (also called neurons). Neurons or nerve fibers are capable of rapidly sending signals to other cells including other neurons, muscle cells, glands, sense cells and many more. These signals are sent in the form of electrochemical waves traveling along thin fibers. The function of these signals (once reaching its ultimate goal) is to stimulate various organs, senses and other parts of the body to properly function (e.g. glands to release secretions, muscles to move). In order for the neurons to reach from their origin (brain) to their ultimate goal many fibers or neurons are typically involved.  These fibers are connected to each other at junctions called synapses. In order for these electrical waves to move from neuron to neuron across a synapse certain chemicals are instantly released (acetylcholine-a neurotransmitter) at these junctions. Once the signal is passed on across the synapse to another neuron, muscle, etc., a second chemical called cholinesterase or acetylcholinesteterase is instantly produced. This enzyme functions to immediately break down the presence of the previously produced acetylcholine at this junction, consequently discontinuing the signal. This process of producing acetylcholine at synapses in body, thus allowing the signal to fire across the synapse and immediately and subsequently breaking down the presence of acetylcholine happen continuously in our body allowing the nervous system and thus body functions occur normally and successfully.

Organophosphorus insecticides and carbamate insecticides are known cholinesterase inhibitors. If these cholinesterase inhibitors are present at a nerve fiber synapses, the proper functions of the nervous system may be interrupted. The presence of these chemical cholinesterase inhibitors prevents the breakdown of acetylcholine. As a result acetylcholine may accumulate and this point resulting in a “jam” or malfunction in the nervous system. For example, if the nerve fiber synapse reaches a muscle and cholinesterase inhibiting chemical such as organophosphorus or carbamate insecticides are present to prevent the breakdown of acetylcholine, the muscle may continue to move due to the presence of the nerve transmitter acetylcholine at the synapse. Electrical impulses will fire away continuously due to the inhibition of cholinesterase by organophosphorus or carbamate insecticides. Continuous firing of the electrical signals can result in uncontrolled, rapid twitching of the affected muscles, difficult or paralyzed breathing, convulsion or in serious cases even death.

The type and degree of cholinesterase inhibition symptoms are dependent on several factors, namely the inherent toxicity of the pesticide or insecticide, the level or amount of exposure, route of exposure (eyes, vs. skin, vs. ingestion) and duration or length of exposure. Even though the signs and symptoms of cholinesterase are quite similar with organophosphorus and carbamate induced poisoning, there are minor but significant differences. The basic difference is that with carbamate induced poisoning the level of cholinesterase in the blood returns to a relative safe level considerably quicker than that typically seen with organophosphorus poisoning. Depending on the level of exposure, carbamates return to normal levels within seven hours, whereas organophosphates take several days to do so.

. A significant factor associated with Organophosphorus and carbamate human poisoning is that the use of these chemicals can have a cumulative effect. An individual may show no visible poisoning effects as the level of cholinesterase builds up in their body. However, once a critical level is reached the symptoms may unravel quite rapidly. However, if an individual experiences a high level to these chemicals, symptoms may occur from that exposure quickly without previous exposure.

Monitoring Requirement of Organophosphorus and Carbamate Pesticides Level in Pest Control

Because of the toxic and accumulative effects of organophosphorus and carbamate pesticides, Federal and California pesticide laws and regulations require certain tests of individuals who work with (handle) these pesticides. If an individual works with an organophosphorus or carbamate with signal words Danger or Warning on a regular basis, and is used for agricultural pest control, he or she is required to be tested and verified every two years for baseline red cell and plasma cholinesterase levels. With new employees, a qualified medical supervisor may accept prior established baseline values. Employers are mandated to guarantee that any employee who was not under previous medical supervision (while employed by the current employer), be tested and meet these required red cell and plasma cholinesterase levels. This indicated requirement must be completed within 3 working days prior to each 30-day period during which the individuals handle these products on a regular basis. Day intervals, additional periodic monitoring must be specified in writing by the certified medical supervisor. If the certified medical supervisor does not make a written recommendation for the continued periodic monitoring of individuals who regularly handle these pesticides, the testing interval must be every 60 days (or every second period). Employers are required by law to keep the following records for three years: the medical supervision agreement, pesticide use records, all recommendations and all test results. These tests must be available for inspection by the employee, the Director of DPR, the county agricultural commissioner, and county and state health officials. If an individual’s red cell or plasma cholinesterase level falls below 80% of their established baseline, the employer must investigate the employee’s work practices, including employee sanitation, pesticide handling procedures and equipment usage.

Organophosphorus and Carbamate Pesticides contain chemicals that are toxic to humans and other animals. They can readily enter the human body via any of number of routes including eyes, skin, breathing and ingestions and subsequently effect cholinesterase activity in the red blood cells plasma and nervous system.

Carbamates insecticides, like organophosphates, vary widely in toxicity and work by inhibiting plasma cholinesterase. Some examples of carbamates are listed. These include aldicarb (Temik), bendiocarb (Ficam), bufencarb, carbaryl (Sevin), carbofuran(Furadan), formetanate (Carzol), methiocarb (Mesurol), methomyl (Lannate, Nudrin), oxamya (Vydate), pinmicarb (Pirimor),and propoxur (Baygon) 

Common Symptoms often associated with Carbamate and Organophosphate Pesticide Poisoning

Mild Symptoms

These typically occur within 4 to 24 hours of contact and include nausea, dizziness, stomach cramps, excessive sweating, fatigue, headache, blurred vision, stomach cramps, and diarrhea. Moderate symptoms-Typically occur within 4 to 24 hours and include chest discomfort, tunnel vision, pinpoint pupils, difficulty in walking, weakness, and any of the mild symptoms that are more severe than might be expected. Severe symptoms after continued daily consumption can be unconsciousness, abdominal cramps, urinating, staggering gait, running nose, severe constriction of pupils, muscle twitching, drooling, breathing difficulty, coma, and death. Carbamates are less persistent in the environment than organochlorines and organophosphates are more acutely toxic, posing a greater risk to anyone exposed to large amounts.

Carbamates – Mode  of Action: Nervous system – acetylcholinesterase inhibition

Carbamates have a very similar mode-of-action mechanism when compared to organophosphates. Carbamates are much more degradable than organophosphates and typically have a lower toxicity. For this reason, carbamates are used more often than organophosphates; but, because less-toxic substitutes are now available, carbamates are also slowly being phased out. 

Neonicotinoids. Mode of Action: Nervous system – acetylcholine receptor agonists

Water extracts of nicotine has historically been used as an insect toxicant. Neonicotinoids are modeled after nicotine and were first created in the 1970s. The first neonicotinoid synthesized was nithiazine and its mode of action was identified in 1984. 

Neonicotinoids work as acetylcholine receptor agonists. Like the previously mentioned pesticides the neonicotinoids target the acetylcholine channel of the nervous system to cause overstimulation of nerve activity. Unlike organophosphates though, which prevent acetylcholinesterase from removing acetylcholine from the receptors and therefore prevent neural activity from being turned off, neonicotinoids target the acetylcholine receptor itself. While acetylcholine is attached to the receptors on the neuron the nerve activity is turned on. Neonicotinoids are able to bind more strongly than acetylcholine to the receptors via the nicotinic acetylcholine receptors. This binding of neonicotinoids to the neuron is irreversible and essentially results in nerve activity being permanently turned on. This results in high levels of nerve activity which cause overstimulation and blocks the receptors, which then causes paralysis and death. In normal function acetylcholinesterase is able to breakdown acetylcholine and turn nerve activity off, However, acetylcholinesterase cannot break down neonicotinoids.

Recently the use of neonicotinoids has been called into question. Common neonicotinoids such as imidacloprid, thiamethoxam and clothianidin have been linked with the decline of the bee population. There has been some evidence that shows that neonicotinoids have had a detrimental effect on the native North American bumblebee. Additionally, some evidence also supports the thesis that pesticides, such as neonicotinoids, have contributed to colony collapse disease of domestic honeybees. Furthermore, a Dutch study found that water contaminated with neonicotinoids had 50% fewer species of invertebrates as opposed to uncontaminated water.

Commonly used neonicotinoids include, Imidacloprid, Dinotefuran, Thiamethoxam, Theiaclopird, Nitenpyram, Clothianidin and Acetamiprid.

Pyrethroids

Mode of Action: Nervous System – Sodium Channel Modulators

Pyrethroids are derived from the naturally occurring pyrethrums found in flowers such as chrysanthemums. Pyrethrums have long been known to have insecticidal properties. They have very low toxicity to animals and degrade quickly so that they do not persist in the environment. Pyrethrums are able to knock down flying insects but due to their very low-level of persistence they are less than ideal for field applications. Pyrethroids are essentially synthesized version of pyrethrum that is more chemically stable so that they persist long enough to be beneficial as an insecticide. First generations of pyrethroid chemicals were not particularly stable but by the third generation pyrethroids were more stable to sunlight. 

Pyrethroids work against insects as sodium channel modulators. Sodium channels on a neuron are typically closed until a neurotransmitter has them opened up to begin nerve activity. Pyrethroids prevent the closure of sodium channels in the axonal membranes. This causes a flood of sodium into the neuron which then activates nerve activity. This overstimulation of nerve activity in insects leads to paralysis and eventually, death.

The most commonly used pyrethroids include allethrin, bifenthrin, cyfluthrin, deltamethrin, permethrin, prallethrin, remethrin, sumithrin and transfluthrin. Pyrethroids have a fairly low toxicity to mammals but are toxic to many invertebrates, including beneficial insects like bees and dragonflies. Pyrethroids are also toxic to fish and other aquatic organisms. Insects such as mayflies, gadflies and other aquatic insects are particularly sensitive to pyrethroids and can be poisoned at such low levels as 4 parts per trillion. Additionally, secondary treatment facilities, such as municipal water treatment centers do not adequately remove pyrethroids from the water.

Mode of Action: Nervous System – Sodium Channel Blocker

Oxadiazine classified insecticides are not toxic in of themselves. Instead it is after the insecticide is broken down within the insect’s body that toxic breakdown products are produced. This is known as bioactivation. The breakdown products of oxadiazine are strong sodium channel blockers. This results in paralysis and blockages of essential nerve activities which will eventually end in death. 

The best known and commonly used oxadiazine is indoxacarb. It is marketed for use mainly against lepidopteran pests. It is also found in cockroach and ant baits, along with some products to kill fleas on dogs and cats. The efficacy of oxadiazine insecticides against insect pests relies very strongly on the toxicity of the breakdown products. Certain insect species do not breakdown oxadiazine into products that are harmful enough to make this insecticide efficient. Oxadiazine has very low toxicity to animals as its breakdown products within mammals are harmless. 

Phenylpyrazole:

Mode of Action: Nervous system – Gamma-amino butyric acid (GABA) Receptor Blocker

Phenylpyrazole is a classification of insecticides that are GABA receptor blockers. As mentioned previously chloride ions inhibit nerve activity. Phenylpyrazole insecticides prevent GABA-gated chloride channels and glutamate-gated chloride (GluCl) channel from opening. This prevents chloride ions from entering the neuron and inhibiting nerve activity, therefore preventing nerve activity from being turned off. This results in hyperexcitation of an insect’s nerves and muscles. Eventually this hyperexcitation will result in death. Phenylpyrazoles have low mammalian toxicity due to the lack of GluCl channel in mammals.

The most well-known and commonly used phenylpyrazole is fipronil. Fipronil is a slow acting poison and therefore good for controlling insects that live in colonies as it allows a poisoned insect to carry the poison back to the group. For example, in cockroaches sufficient amounts of fipronil have been found in feces and carcasses to kill other cockroaches in the same nesting site. For this reason fipronil has been used in the control of ants, cockroaches and wasps. However it is also marketed in products designed to target Lepidoptera (trade name Regent), locusts (trade name Adonis), and ticks and fleas for cats and dogs (trade names TopSpot, Fiproguard, Flevox, and PetArmor). A relatively high degree of resistance of fleas to products containing this pesticide has been reported-at least according to my vet.

Fipronil is highly toxic to many invertebrates, including crustaceans, insects and zooplankton. It is also toxic to rabbits, fringe-toed lizards, some gallinaceous birds, and many fish. Fipronil has been found to have non-target effects on many animals including some beetles, parasitic wasps and bees. In fact, evidence suggests that fipronil may play a large part in colony collapse disorder seen in bees and the European Food Safety Authority banned the use of fipronil in 2013 for use on corn and sunflowers within the European Union.

Avermectins

Mode of Action: Nervous system – Glutamate Receptor Stimulator

Avermectin enhances the effect of glutamate in the glutamate-gated chloride channels found in insects. This results in an influx of chloride ions into the insect’s neurons. Chloride reduced nerve activity and excess amount of chloride in neurons results in paralysis of the invertebrate neuromuscular system. In other words, because avermectin opens the neurons to an influx of chloride ion it keeps nerve activity turned off. As mammals do not possess glutamate-gated chloride channels avermectins are considered non-toxic to them.

The most commonly used avermectins include ivermectin, piperazine, and dichlorovos. There has been resistance to avermectin reported so restrictions on its use have been advised. 

Cellular Poisons

Pyrrole: Mode of Action: Cellular Poison – Adenosine Triphosphate Disruption

Pyrroles are bioactivated by enzymes that are within insects and in toxic byproducts. These byproducts disrupt the production of adenosine triphosphate. This causes disruption of ATP within the mitochondria of the cell which results in cell death and ultimately death of the organism. The best known pyrrole insecticide is chlorfenapyr. It has been authorized for use by the EPA in 2001 in greenhouses on non-food crops. By 2005 the EPA had established residue limits for chlorfenapyr on all food commodities. In general pyrroles have a lower toxicity for mammals, however in 2016; a report found that 31 people had died in Pakistan due to food being spiked with chlorfenapyr. 

Amidinohydrazone

Mode of Action: Cellular poison – Mitochondrial Disruptor

Amidinohydrazone attacks the mitochondria within the cells. Insect poisoned with this class of insecticide exhibit a limp paralysis. As the mitochondria created the energy needed for normal bodily functions, poisoned insects lose more and more energy until, ultimately, they die. One of the most commonly used insecticides of this class has the active ingredient hydramethylnon. 

Muscular Poisons

Diamide: Mode of Action: Cellular Poison – Calcium Channel Stimulator

Diamide targets the calcium channels within muscles, causing uncontrolled calcium release. Calcium causes muscle contraction. Insect poisoned with diamide exhibit “contractile” paralysis in the early stage of exposure and then symptoms that are very similar to inhibitory neurotoxins at later stages. Insects have a much higher sensitivity to diamide than mammals; as a result this chemical is considered low toxicity to humans. 

Miscellaneous Pesticides

Rodenticides

There are a number of rodenticides that are termed as anticoagulants in nature. As their name implies, when a rodent (or human, for that matter) receives significant exposure to these chemicals (mainly orally) the ability of the blood to clot is reduced. In addition these chemicals also cause capillaries in the body to break. The liver (in rodents and humans) normally produces enzyme that allows our bodies to recycle Vitamin K. Vitamin K is required to minimize blood clotting agents that protect mammals from excessive bleeding. Anticoagulant pesticides basically prevent this enzyme from properly functioning. Of course, Vitamin K is stored in the body, but with excessive exposure to an anticoagulant, internal bleeding will result. There is an antidote to anticoagulant poisoning, namely Vitamin K.

These pesticides can create a risk for accidental poisonings to a degree. They are specifically designed to kill mammals and as a result often their toxicity frequently is very similar for the target rodents and humans. In addition rodents commonly share the same environments with humans and other mammals; as a result the risk of accidental exposure is a considerable issue when placing of baits for the rodents.

There are 2 active ingredients of the indandione family of rodenticides, namely chlorophacinone and diphacinone. The indandiones are not only anticoagulants, but they also uncouple oxidative phosphorylation (energy generation) in mammals. Both of these active ingredients are sold as general restricted-use products on the market. Chlorophacinone tends to be formulated as a low percentage ready-use-product and has the signal word “CAUTION” on the label whereas some of their restricted products carry the signal words “WARNING” on their labels.

Both products are classified as restricted because the EPA considers them to be high in acute oral toxicity.

Tests indicate that diphacinone is not mutagenic, and there are no data currently available on its reproductive, growth retardation, delayed mental development, and cancer producing effects. Studies with cattle indicate a high tolerance to diphacinone; it is used in Latin America for controlling vampire bats preying on cattle.

Courmarin and Indandiones

Ecologically, the main concern with the rodenticides, coumarins and indandiones, is secondary poisoning. Mortality is a likely result in wildlife that feed on rodents that have ingested these compounds (secondary poisoning).

Zinc Phosphide
 
Zinc phosphide reacts with atmospheric moisture to slowly release phosphine (not phosgene), a toxic and flammable gas with an odor similar to garlic or onions. When formulated as grain bait and exposed to normal atmospheric conditions the gas that is produced presents little hazard. However when exposed to acidic conditions (as in the stomach) the gas is released quickly accounting for the toxic nature of the chemical. Although zinc phosphide baits have a strong pungent odor this seems to attract rodents, especially rats, and apparently makes the bait unattractive to some other animals. Zinc phosphide baits are typically grey in coloration.

Animals that consume lethal amounts of zinc phosphide typically die within 30 hours. Early symptoms include nausea, tightness of the chest, excitement and an overall feeling of cold and vomiting of a black colored stomach contents and the garlic smell of phosphine gas. Advanced symptoms include convulsions, paralysis, coma and death due to respiratory failure. If symptoms extend for several days intoxication occurs with resultant heavy liver damage. Typically if an individual lives for 3-days recovery is complete. 

The dust at the bottom of zinc phosphide container creates a potential hazard and every precaution should be maintained to avoid inhaling this material when pouring from the original packaging. Zinc phosphide bait should not be handled without gloves. Oils and other liquid are used in the preparation of some bait. As a result repeated handling can result in small amounts being absorbed through the skin. Repeated absorption to phosphine gas can result in symptoms at a later date.

Zinc phosphide can result in severe irritation if consumed. It reacts with water and especially so with stomach juices to release phosphine gas which can quickly enter the mammalian circulatory system and subsequently affect the lungs, liver, kidneys, heart and central nervous system. Zinc phosphide is easily absorbed via the skin or if inhaled from fumes. With repeated exposure, it readily accumulates in the body to serious levels. 

Indications of relatively mild zinc phosphide poisoning are stomach pains and diarrhea. More severe poisoning symptoms can include, tightness of the chest, throwing up, excitement, feeling cold, passing out, coma and even death due to pulmonary edema and liver damage. There is no antidote. A plus is that it is slow-acting thus giving time to seek medical treatment. It also naturally induces vomiting and is it is quickly removed from the body. 

Strychnine

Strychnine is mainly used as gopher bait. It is an extremely toxic material to mammals with an Acute Oral LD (AOLD50) of around to 6. A lethal dose of this natural toxin is as little as 15 mg in children. It is not easily absorbed through the skin nor does it accumulate in the human body. When ingested, it acts on the central nervous system (mainly the spinal cord) within 10 to 30 minutes. Violent convulsions occur, causing breathing to stop. This material has an extremely bitter taste when ingested even in very small amounts.

There is no antidote for strychnine poisoning. Decontamination therapies carry the risk of aspiration and convulsions—use with caution, if at all.  With strychnine poisoning, it is significant to locate the victim in a warm, dark room. In the case of strychnine poisoning medical help should be brought to the victim rather than moving the victim to a medical center which may again trigger convulsions. In recent years this chemical has fallen off the market considerably.

Fumigants
 
Various types of fumigants produce differing physiologic effects. Headache, dizziness, nausea and vomiting are common early signs and symptoms of excessive exposure. 

Sulfuryl fluoride (product Vikane) is the most commonly used fumigant for control of drywood termites and various wood boring beetles. It is a clear, tasteless, odorless gas with poisoning symptoms including depression, slowed gait, slurred speech, nausea, vomiting, stomach pain, drunkenness, itching, numbness, twitching, and seizures. Inhalation may be fatal due to respiratory failure. Inhalation of high concentrations may cause respiratory tract irritation. Skin contact with sulfuryl fluoride normally poses no hazard, but contact with liquid sulfuryl fluoride can cause pain and frostbite due to rapid evaporation.

Aluminum phosphide (Phostoxin, Gastoxin, Fumitoxin) is commonly used for grain fumigation and control of burrowing rodents. It can affect cell function, liver and lungs. A sensation of cold, chest pains, diarrhea and vomiting has been reported with mild exposure. More serious cases may result in cough, chest tightness, difficult breathing, weakness, thirst and anxiety. Extreme exposure is indicated by stomach pain, loss of coordination, blue skin color, limb pain, enlarged pupils, choking, fluid in the lungs and stupor. Severe poisonings lead to seizures, coma and death.

To treat victims of fumigant exposure, remove them to fresh air immediately, keep them quiet and in a semi-reclining position. Mouth- to-mouth resuscitation or cardiopulmonary resuscitation (CPR) should be applied if breathing or pulse stops. Anyone attempting to rescue a person suffering from fumigant exposure should be properly equipped with self-contained breathing apparatus. Minimum physical activity limits the likelihood of pulmonary edema, a medical emergency characterized by the accumulation of abnormally large amounts of fluid in the lungs. If skin is contaminated, flush with water for at least 15 minutes. Seek medical attention immediately. Time is particularly critical in fumigant poisonings; victims must receive prompt medical attention. 

Miscellaneous Pesticides 

Insecticide Repellents

DEET (diethyltoluamide) is the main ingredient in repellents used against mosquitoes and other blood feeding arthropods. Products such as OFF and MGK are effective and generally well-tolerated when applied to human skin. In some situations use of this product has resulted in skin irritation and worsening of preexisting skin conditions. It is quite irritating when coming in contact with the eyes. Serious symptoms have been reported, especially under hot, humid situations or if used on skin areas that are in direct contact during sleep. In situations like this the skin can become red, tender and blistered. Permanent scarring can result in severe cases. If used it should only be applied to clothing and products containing lower concentrations are advisable. It should be noted that recently newer formulations of DEET are readily available. These are microencapsulate thus have a longer residual and are much more comfortable to use besides presenting less chances of side effects.

Pesticide Resistance

Worldwide, more than 500 species of insects and related arthropods are resistant to insecticides. In addition over 270 weed species, over 150 plant pathogens, and a few handfuls of species of rats are resistant to pesticides that at one time controlled them. Resistance to a pesticide results when the population of a given pest (weed, insect, rodent, etc.) is continually exposed to a pesticide. With initial exposures great control may occur but after multiple exposures a few of the pest are not killed. Those few that survive these initial treatments frequently have done so via the fact that they already possess one or more genes that function to resist or survive the applications. With repeated applications and higher rates of the same or related insecticide, a number of these pests are killed but some or possibly more resistant insects will survive. Of course insects typically have a tremendous reproductive capacity and offspring of these surviving pests pass the genetic composition of their parents. These offspring, many of which will inherit this genetic ability to withstand the exposure to the insecticide, will eventually increase greater number with each succeeding generation of the population. 

Pesticide resistance could be thought of as a type of evolution-survival of the fittest. Where evolution of a species may take many thousands of years, resistance in insects occurs relatively rapidly. This is due to the fact that most of our pest insects have a tremendous reproductive capacity (relatively short life cycles and lay lots of eggs). Some mosquitoes can complete one life cycle in less than a week, as a result many generations can be completed in a single season or year. It follows that repeated applications of an insecticide may readily eliminate all susceptible insects in a given population by selecting out those individuals that carry a resistant gene. In a relatively short period, some of or even an entire population of a given insect can become resistant to a given pesticide. The more frequently an insect population is treated with a pesticide, especially a broad-spectrum pesticide, the more quickly it will develop resistance; with the right preconditions, insect populations will almost always develop a resistance to a given pesticide.

In most case inherited pesticide resistance is the presence of genes that allows the resistant insect to produce an enzyme that detoxifies the active ingredient prior to having it effect, namely death.

Resistance in a pest may develop to only a single insecticide. On the other hand, it is common for an insect that has developed resistance to one insecticide to also be resistant (or develop resistance more rapidly) to other insecticides that exhibit the same mode of action.  A well-known example is the house fly, Musca domestica. In the 1950s populations of this developed resistant to DDT and then decades later exhibited resistance with no previous exposure to pyrethroids. Of courses the answers are that DDT and pyrethroids have the same mode of action. This type of situation is known as cross-resistance. Closely related to the process of cross resistance is the phenomenon of multiple resistances. Multiple resistances occur when insect populations resist two or more insecticide classes with unlike modes of action. This is the result of expressing multiple resistance mechanisms. This can occur if insecticide A is used until the effected insects display a resistance and then Insecticide B is used and the insect population becomes resistant to that one. An extreme example of cross resistance is with local populations of Colorado potato beetle where over time this beetle developed resistance to more than 50 insecticides with variety of modes of action. This type resistance is less common than cross resistance but certainly creates concern due to the fact that it tremendously reduces the number of insecticides that can be used to control a given pest.

Due to both types of resistance, pests that were once major threats to human health and agriculture but that at one point were under good control by pesticides are now on the rebound. Without a doubt one of the biggest problem mosquitoes that transmit malaria are now resistant to virtually all pesticides used against them. Slightly after WWII malaria was eliminated by 2/3 of the world where it previously occurred with the use of DDT. This problem is made much worse due to the fact the Plasmodia that causes malaria has also become resistant to drugs used to treat the disease in humans. The corn earworm, one of the most important worldwide pests that feed on the fruiting bodies of corn, cotton, tomatoes, tobacco and peanuts is now resistant to multiple pesticides.

Combating Resistance

There are multiple techniques that can be used to correct or avoid the problem created from pesticide resistance once it develops in a pest. The most obvious method is to use a different pesticide. This by far the most effective the second pesticide is in a different chemical class that has a different mode of action against the pest. Of course, this depends on the availability of pesticides with different modes of action. Although probably not the best solution, but such an approach would allow a given pest to be controlled until more effective management practices can be developed for control of the pest. 

Pest species developing resistance to pesticides seem to be increasing at an alarming rate. On the other hand, the availability of pesticide products is on a decrease. The costs of developing a pesticide (i.e., the cost research required to attain EPA and States registration) are tremendous. Many millions of dollars are put into the development of chemicals, most of which that may never become marketable products. The United State Environmental Protection Agency and DPR have banned and restricted the use of many pesticides in the past two decades. Additionally the supply of existing registered pesticide products has shrunk as a result of the EPA’s registration of pesticides which frequently includes additional testing of these products to determine if their use possibly endanger the health of humans and our environment. There is little doubt that these requirements are needed. However, the cost of complying with EPA’s reregistration requirements for testing, plus the subsequent reregistration fees, reportedly is having a heavy impact on the current and future availability of some these products. 

Management practices that influence the development of resistance includes the method by which materials are applied, how frequently these products are used, the length of persistence in the field, treatment thresholds, and strategies for the use of available products. Pest management is practical and works in concert with pesticide-use strategies to lessen resistance selection. Pesticide-use strategies work best when initiated as a new pesticide becomes available. Pesticide developers, integrated pest management experts, and growers now recognize that using resistance management from the beginning works best. Determining and using baseline susceptibilities, determining possible resistance situations in advance, and developing and using pesticide-use strategies to retard the development of resistance are the function of manufacturers and integrated pest management experts. Biology and economics sound resistance management strategies offered pre-sale give growers the best hope for this phenomenon. Pesticide-use strategies frequently include management by moderation, rotation and mixtures, and saturation.

Moderation

An obvious approach of slowing down the development of resistance to a given pesticide is minimizing its use. Of course this process is one of the mainstays of integrated pest management practices. These include using established treatment thresholds, limiting spraying procedures to specific pest generations or growth stages, planting or maintaining unsprayed wild host reservoirs to serve as refuges for genetically susceptible pest individuals, and utilizing pesticides that have shorter residual or lower toxicity to important beneficial to name a few. Moderation should be used to the fullest extent that will still provide commercially acceptable results. 

Rotation of given products, and in some situations mixtures, are the mainstay of pesticide-use strategies due to the fact that an individual pest species is less likely to be resistant to 2 or more differing classes of active ingredients. At least in theory, the majority of individual pest species are resistant to one pesticide. For example mixtures of fungicides have been used with a considerable degree of success to fight disease resistance, although the overall degree of cost decreases the attractiveness of this approach. On the other hand mixtures of insecticides and miticides have normally produced less than successful results. 

Saturation, can be defined as the use of higher application rates in order to control resistant populations of a given pest species. This is obviously the least attractive resistance management approach, although it has seen success in certain situations such as to manage resistance to DMI fungicides. This technique should only be used as a last resort provided there is a lack of effective techniques, or labeled alternatives. In situations like this, higher rates will likely provide temporary control, although at greater cost and in the end produce increased resistance. Synergists when available can increase the toxicity of pesticides and have on occasion been used to increase efficacy of resistance-prone pesticides. As seen in the use of saturation rates, synergists typically provides only short-term benefits.

The Insecticide Resistance Action Committee IRAC) has been formed. They have grouped insecticides by mode of action. As long as applicators avoid using the same grouping for each application and instead alternate by grouping this should help alleviate resistance issues. The pesticides and their grouping are listed below:

Group 1 – Nerve and Muscle – Acetylcholinesterase (ACHE) Inhibitors: Carbamates, Organophosphates.

Group 2 – Nerve and Muscle – GABA-gated Chloride channel blockers: Cyclodiene organochlorines, Phenylpyrazoles (Fiproles).

Group 3 – Nerve and Muscle – Sodium channel modulators: Pyrethroids, Pyrethrins, DDT, Methoxychlor.

Group 4 – Nerve and Muscle – Nicotinic acetylcholine receptor (NaChr) competitive modulators: Neonicotinoids, Nicotine, Sulfoximines, Butenolides, Mesoionics.

Group 5 – Nerve and Muscle – Nicotinic acetylcholine receptor (NaCHR) allosteric modulators: Spinosysns.

Group 6 – Nerve and Muscle – Glutamate-gated chloride channel (GluCl) allosteric modulators: Avermectins, Milbemycins

Group 7 – Growth – Juvenile hormone mimics: Juvenile hormone analogues, Fenoxycarb. Pyriproxyfen

Group 8 – Unknown or Non-Specific – Miscellaneous non-specific (multi-site) inhibitors: Alkyl halides, Chloropicrin, Fluorides, Borates, Tartar emetic, Methyl isothiocyanate generators

Group 9 – Nerve and Muscle – Chordotonal organ TRPV channel modulators:Pyridine azomethine derivatives

Group 10 – Growth – Mite growth inhibitors, Clofentezine, diflovidazin, etoxazole, Etoxazole

Group 11 – Midgut – Microbial disruptors of insect midgut membranes: Bacillus thuringiensis and the insecticidal proteins they produce, Bacillus sphaericus

Group 12 – Respiration – Inhibitors of mitochondrial ATP synthase: Diafenthiuron, Organotin miticides, Propargite, Tetradifon

Group 13 – Respiration – Uncouplers of oxidative phosphorylation via disruption of the proton gradient: Chlorfenapyr, DNOC, sulfluramid

Group 14 - Nerve and Muscle – Nicotinic acetylcholine receptor (NaCHR) channel blockers: Nereistoxin analogues

Group 15 – Growth – Inhibitors of chitin biosynthesis, type 0:Benzoylureas

Group 16 – Growth – Inhibitors of chitin biosynthesis, type 1: Buprofezin

Group 17 – Growth – Molting disruptor, dipteran:Cyromazine

Group 18 – Growth – Ecdysone receptor agonists: Diacylhydrazines

Group 19 - Nerve and Muscle – Octopamine receptor agonists:Amitraz

Group 20 – Respiration – Mitochondrial complex III electron transport inhibitors: Hydramethylnon, Acequinocyl, Fluarypyrim, Bifenazate

Group 21 – Respiration – Mitochondrial complex I electron transport inhibitors: Meti acaricides and insecticides, Rotenone

Group 22 - Nerve and Muscle – Voltage-dependent sodium channel blockers: Oxadiazines, Semicarbazones

Group 23 – Growth – Inhibitors of acetyl Coa carboxylase, Tetronic and tetramic acid derivatives

Group 24 – Respiration – Mitochondrial complex IV electron transport inhibitors: Phosphides, Cyanides

Group 25 – Respiration – Mitochondrial complex II electron transport inhibitors: Beta-ketonitrile derivatives, Carboxanilides

Group 28 - Nerve and Muscle – Ryanodine receptor modulators: Diamides

Group 29 - Nerve and Muscle – Chordotonal organ modulators – undefined target site: Flonicamid

Group UN - Unknown or Non-Specific – Compounds of unknown or uncertain MoA: Azadirachtin, Benzoximate, Bromopropylate, Chinomethionat, Dicofol, GS-Omega/Kappa HXTX – HV1A peptide, Lime sulfur, Pyridalyl, Sulfur

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Questions. Continuing Education.

1. The United States Environmental Protection Agency and in many cases individual states (including California) require a pesticide developer to submit massive amounts of data based on up to 150 tests prior to that product's approval for use.

2. The front panel of all pesticide labels must carry the statement, "KEEP OUT OF REACH OF CHILDREN. 

3. Pesticide exposure incidents occur in greater frequency to children under the age of two years than to older children, teens, and adults on an annual basis. It is well-reported that infants and small children are considerably more sensitive to these toxicants and even inactive ingredients in pesticides than are adults

4. Labels of pesticide products bearing the DANGER signal word due to skin and eye irritation potential will not carry the word POISON or the skull-and-crossbones image.

5. The only pesticide products where signal words are not required on a label are those that occur in the lowest toxicity category by all possible routes of exposure, namely oral, dermal, inhalation, and other effects like eye irritation.

6. The most recent information on the protectiveness of these materials in pesticide gloves indicate that nitrile, butyl, and neoprene give good protection for both dry and liquid pesticides but neoprene is not recommended when applying fumigants.

7. The Environmental Hazard portion of the pesticide label discusses the type of potential hazards and the needed precautions needed to avoid injury or damage to a variety of non-target organisms and/or the environment.

8. The front panel of certain labels will describe pesticide formulations. The type of formulation may be either be indicated by an abbreviation (e.g. .G = Granular, EC or E=emulsifiable concentrate, M=microencapsulation), or spelled out. There are many other types of formulations, but these are a few of the more common types. 

9. Knowing a particular type of formulation is helpful because it provides insight about the types of application equipment needed, product's handling properties and the potential hazard of a given formulation.

10. According to the American Association of Poison Control Centers, pesticide exposure incidents occur in greater frequency to children under the age of six years than to older children, teens, and adults on an annual basis

11. An infant’s brain, nervous system, and other organs are still in the process of developing well after birth. 

12. Most wettable powders contain a high % of active ingredient and are basically a dust. As a result there is a higher inhalation hazard to applicator when measuring and mixing the concentrated powder.

13. Insect growth regulators, or IGRs, are synthetically produced hormone mimics. IGRs prevent insects from reaching productive age by inhibiting essential hormones. IGRs can be divided into two groups: hormonal regulators that disrupt metamorphosis and disruptors of chitin synthesis. IGRs do not kill adult insects.

14. Organophosphorus insecticides and carbamate insecticides are known cholinesterase inhibitors. If these cholinesterase inhibitors are present at a nerve fiber synapses, the proper functions of the nervous system may be interrupted. The presence of these chemical cholinesterase inhibitors prevents the breakdown of acetylcholine. As a result acetylcholine may accumulate and this point resulting in a “jam” or malfunction in the nervous system. 

15. The applicator increases the potential for poisoning of pesticides moved from a hand (1.3) to a sweaty forehead (4.2) or to the genital area (11.8). At the very highest rate (groin), the absorption of a pesticide through the skin may be more dangerous than if swallowed!

16. The toxicity of the active ingredient in a product does not always correlate directly to potential hazard of that product. The hazard may vary considerably depending on the formulation of the product, concentration of the toxicant in the product, method of application and other factors. 

17. Emusifiable concentrates are readily absorbed through skin: plus their high percentage of toxicant prior to mixing typically necessitates the use of protective equipment during mixing and loading. The solvents in emusifiable concentrates may lead to rubber or plastic hoses, gaskets, and pump parts to break down over time. In addition these formulations are capable pitting or discoloration of painted finishes. 

18. Leather and cotton gloves can be more hazardous than using no protection at all simply because they easily absorb pesticides and as a result hold them close to the skin for extended periods of time. 

19. Insect growth regulations work equally effective on both the immature and adult insects.

20. Juvenile hormone (JH) mimics are not quite as active in their effects as the natural hormone. However, if levels of JH mimics remain high, the insect does not advance in stage. If you prevent the insect from becoming adults, there can be no reproduction. After exposure to JH, insect death typically occurs when insects molt from the last instar to the adult.

21. Generally pesticide tolerances on agricultural produce are typically set at least 40 times less than the maximum dose that had a no observable effect level (NOEL) in test animals.

22. Common neonicotinoids such as imidacloprid, thiamethoxam and clothianidin has been linked with the decline of the bee population. There has been some evidence that shows that neonicotinoids have had a detrimental effect on the native North American bumblebee. Additionally, some evidence also supports the thesis that pesticides such as neonicotinoids has contributed to Colony Collapse Disease of domestic honeybees.

23. DDT was heavily used in the 1940s and 1950s, particularly during World War II to control vector insects of typhus, nearly eliminating the disease in Europe. DDT was also used during this time for the control of malaria and dengue in the South Pacific. DDT also played an important role in the elimination of malaria from North America and Europe. 

24. The basic difference between pesticide poisonings is that with carbamate induced poisoning the level of cholinesterase in the blood returns to a relative safe level considerable quicker that that typically seen with organophosphorus poisoning.

25. Pyrethroids work against insects as sodium channel modulators. Sodium channels on a neuron are typically closed until a neurotransmitter has them opened up to begin nerve activity. Pyrethroids prevent the closure of sodium channels in the axonal membranes. This causes a flood of sodium into the neuron which then activates nerve activity. This overstimulation of nerve activity in insects leads to paralysis and eventually, death.

26. Bacillus thurengensis (Bt) is a bacterium that naturally occurs in soil. It produces spores and crystalline proteins that have been used to control insect pests since the 1920s. There are different forms of this bacterium that are currently used as specific insecticides; these are present in a variety of trade name such as ThuricideBerliner (B.t. variety kurstaki): Dipel, Thuricide, Bactospeine, Leptox, Novabac, Victory, Certan (B.t. variety aizawa). Teknar (B.t. variety israelensis).

27. Zinc phosphide reacts with atmospheric moisture to slowly release phosphine (not phosgene), a toxic and flammable gas with an odor similar to garlic or onions. When formulated as grain bait and exposed to normal atmospheric conditions the gas that is produced presents little hazard.  However when exposed to acidic conditions (as in the stomach) the gas is released quickly accounting for the toxic nature of the chemical.

28. Strychnine is mainly used as gopher bait. It is an extremely toxic material to mammals with an AOLD50 of around 4 to 6. A lethal dose of this natural toxin is as little as 15 mg in children. It is not easily absorbed through the skin nor does it accumulate in the human body. When ingested, it acts on the central nervous system (mainly the spinal cord) within 40 t0 60 to 30 minutes.

29. The dust at the bottom of zinc phosphide container creates a potential hazard and every precaution should be maintained to avoid inhaling this material when pouring from the original packaging. Zinc phosphide bait should not be handled without gloves. Oils and other liquid are used in the preparation of some bait. As a result repeated handling can result in small amounts being absorbed through the skin. Repeated absorption to phosphine gas can result in symptoms at a later date.  

30. DEET, diethyltoluamide is the main ingredient in repellents used against mosquitoes and other blood feeding arthropods. Products such as OFF and MGK are effective and generally well-tolerated when applied to human skin. In some situations use of this product has resulted in skin irritation and worsening of preexisting skin conditions. It is quite irritating when coming in contact with the eyes. Serious symptoms have been reported, especially under hot, humid situations or if used on skin areas that are in direct contact during sleep.

31. Worldwide, more than 300 species of insects and related arthropods are resistant to insecticides. In addition over 170 weed species, over 150 plant pathogens, and a few handfuls of species of rats are resistant to pesticides that at one time controlled them.

32. An obvious approach of slowing down the development of resistance to a given pesticide is minimizing its use. Of course this process is one of the mainstays of integrated pest management practices. These include using established treatment thresholds, limiting spraying procedures to specific pest generations or growth stages, planting or maintaining unsprayed wild host reservoirs to serve as refuges for genetically susceptible pest individuals, and utilizing pesticides that have shorter residual or lower toxicity to important beneficial species. Pests are developing resistance to pesticides seem to be increasing at an alarming rate. On the other hand, the availability of pesticide products is on a decrease. The costs of developing a pesticide (i.e., the cost research attain EPA and States registration) are tremendous. Many millions of dollars are put into the development of chemicals, most of which that may never become marketable products.

33. Resistance in a pest may develop to only a single insecticide. On the other hand, it is common for an insect that has developed resistance to one insecticide to also be resistant (or develop resistance more rapidly) to other insecticides that exhibit the same mode of action.

34. The Insecticide Resistance Action Committee IRAC) has grouped insecticides by mode of action. As long as applicators avoid using the same grouping for each application and instead alternate by grouping this should help alleviate resistance issues.

35. Saturation, can be defined as the use of higher application rates in order to control resistant populations of a given pest species. This is obviously the least attractive resistance management approach, although it has seen success in certain situations such as to manage resistance to DMI fungicides.

36. The use of the saturation technique to slow down the development of pesticide resistance should only be used as a last resort provided there is a lack of effective techniques, or labeled alternatives.

37. With saturation higher rates will likely provide temporary control, although at greater cost and in the end produce increased resistance. 

38. Synergists when available can increase the toxicity of pesticides and have on occasion been used to increase efficacy of resistance-prone pesticides. As seen in the use of saturation rates, synergists typically provides only short-term benefits.

39. A closely related to the process of cross resistance is the phenomenon of multiple resistances. Multiple resistances occur when insect populations that resist two or more insecticide classes with unlike modes of action. This is the result of expressing multiple resistance mechanisms.

40. An obvious approach of slowing down the development of resistance to a given pesticide is minimizing its use. Of course this process is one of the mainstays of integrated pest management practices. These include using established treatment thresholds, limiting spraying procedures to specific pest generations or growth stages, planting or maintaining unsprayed wild host reservoirs to serve as refuges for genetically susceptible pest individuals, and utilizing pesticides that have shorter residual or lower toxicity to important beneficial to name a few. Moderation should be used to the fullest extent that will still provide commercially acceptable results. 

41. Pyrroles are bioactivated by enzymes that are within insects and in toxic byproducts. These byproducts disrupt the production of adenosine triphosphate. This causes disruption of ATP within the mitochondria of the cell which results in cell death and ultimately death of the organism.

42. Pyrethroids work against insects as sodium channel modulators. Sodium channels on a neuron are typically closed until a neurotransmitter has them opened up to begin nerve activity. Pyrethroids prevent the closure of sodium channels in the axonal membranes. This causes a flood of sodium into the neuron which then activates nerve activity. This overstimulation of nerve activity in insects leads to paralysis and eventually, death.