Essential Pesticide Readings for Beginners (四)

1. Pesticide Toxicity and hazard

In terms of pesticide safety, there is an important difference between the words "toxicity" and "hazard". Toxicity refers to inherent poisonous potency of a material. Its toxicity is evaluated in toxicology laboratories and is always expressed in quantitative terms such as LC50 (lethal concentration-50, the concentration at which a material will kill 50% of some reference organism. Hazard, on the other hand, depends not only on the toxicity of a material, but also on the risk of toxic exposure when used. In simple terms, remember that toxicity is the capacity of a substance to produce illness or death, hazard is a function of toxicity and exposure. Together, toxicity and hazard information can be used to determine risk.

There is a greater potential for harmful effects to humans from highly toxic pesticides than from pesticides that are less toxic. However, the concentration of the pesticide in a formulation, the length of human exposure to a pesticide, and the route of entry into the human body are equally important in the potential for poisoning. Although a pesticide applicator will have little control over the toxicity of a pesticide, he or she will have significant control over hazards associated with pesticide use. A sealed container of a very toxic pesticide presents little hazard to a pesticide technician before the seal is broken. Even when the container is opened, the hazard (or risk?) may be small if the technician is wearing protective clothing, gloves, and eye protection. However, if the container is leaking, or if the technician is not using protective gear, the hazard can be high.

2. Types of toxicity studies required for pesticides

The toxicity of a pesticide is its capacity or ability to cause injury or illness. The toxicity of a particular pesticide is determined by subjecting test animals to varying dosages of the active ingredient (a.i.) and each of its formulated products. The active ingredient is the chemical component in the pesticide product that controls the pest. The two types of toxicity are acute and chronic.

Acute toxicity of a pesticide refers to the chemical’s ability to cause injury to a person or animal from a single exposure, generally of short duration. The four routes of exposure are dermal (skin), inhalation (lungs), oral (mouth), and eyes. Acute toxicity is determined by examining the dermal toxicity, inhalation toxicity, and oral toxicity of test animals. In addition, eye and skin irritation are also examined.

Acute toxicity is measured as the amount or concentration of a toxicant-the a.i.-required to kill 50 percent of the animals in a test population. This measure is usually expressed as LD50 (lethal dose 50) or LC50 (lethal concentration 50). Additionally, the LD50 and LC50 values are based on a single dosage and are recorded in milligrams of pesticide per kilogram of body weight (mg/kg) of the test animal or in parts per million (ppm). LD50 and LC50 values are useful in comparing the toxicities of different active ingredients and different formulations containing the same active ingredient. The lower the LD50 or LC50 of a pesticide product, the greater its toxicity to humans and animals. Pesticides with a high LD50 are the least toxic to humans if used according to the directions on the product label.

The chronic toxicity of a pesticide is determined by subjecting test animals to long-term exposure to the active ingredient. Any harmful effects that occur from small doses repeated over a period of time are termed chronic effects. Some of the suspected chronic effects from exposure to certain pesticides include birth defects, production of tumors, blood disorders, and neurotoxic effects (nerve disorders). The chronic toxicity of a pesticide is more difficult to determine through laboratory analysis than acute toxicity.

Products are categorized on the basis of their relative acute toxicity (their LD50 or LC50 values). Pesticides that are classified as highly toxic (Toxicity Category I) on the basis of either oral, dermal, or inhalation toxicity must have the signal words DANGER and POISON printed in red with a skull and crossbones symbol prominently displayed on the front panel of the package label.

2.1 Acute toxicity

Acute toxicity usually results from a single exposure to a high dose or concentration of a toxicant, which can be either oral, dermal, or through inhalation. The acute toxicity is the basis for pesticide classifications on product labels. It is defined as the amount of a pesticide’s active ingredient that kills 50 percent of the test population in a short period of time, referred to as LD50 (lethal dose 50) or LC50 (lethal concentration 50). Toxicity increases as the LD50 or LC50 decreases.

Products are categorized on the basis of their relative acute toxicity (their LD50 or LC50 values). Pesticides that are classified as highly toxic (Toxicity Category I) on the basis of either oral, dermal, or inhalation toxicity must have the signal words DANGER and POISON printed in red with a skull and crossbones symbol prominently displayed on the front panel of the package label. The Spanish equivalent for DANGER, “PELIGRO,” must also appear on the labels of highly toxic chemicals. The acute (single dosage) oral LD50 for pesticide products in this group ranges from a trace amount to 50 mg/kg. For example, exposure of a few drops of a material taken orally could be fatal to a 150-pound person.

Some pesticide products have the signal word DANGER without the skull and crossbones symbol. This is because possible skin and eye effects are more severe than suggested by the acute toxicity (LD50) of the product.

Pesticide products considered moderately toxic (Toxicity Category II) must have the signal word WARNING and “AVISO” (the Spanish equivalent) displayed on the product label. In this category, the acute oral LD50 ranges from 50 to 500 mg/kg. A teaspoon to an ounce of this material could be fatal to a 150-pound person.

Pesticide products classified as either slightly toxic or relatively nontoxic (Toxicity Categories III and IV) are required to have the signal word CAUTION on the pesticide label. Acute oral LD50 values in this group are greater than 500 mg/kg. An ounce or more of this material could be fatal to a 150-pound person.

Despite the fact that some pesticide products are considered only slightly toxic or relatively nontoxic, all pesticides can be hazardous to humans, animals, other organisms, and the environment if the instructions on the product label are not followed. Use the pesticide only as recommended by the manufacturer. As the applicator, you are legally responsible for any misuse of a pesticide.

Table 1 summarizes the LD50 and LC50 values for each route of exposure for the four toxicity categories and their associated signal word. For example, an active ingredient with a dermal LD50 of 1,000 mg/kg would be in Toxicity Category II with a WARNING signal word. Keep in mind, an active ingredient may have a high LD50 placing it in a Toxicity Category II, III, or IV but also have corrosive eye/skin effects that take priority and place it in Toxicity Category I.

Table 1  Toxicity Categories for Active Ingredients

Routes of Exposure


Category I

Toxicity Category II


Category  III

Toxicity Category IV

Oral LD50

Up to and including 50 mg/kg

50–500 mg/kg

500–5,000 mg/kg

>5,000 mg/kg

Inhalation LC50

Up to and including 0.2 mg/l

0.2–2 mg/l

2–20 mg/l

>20 mg/l

Dermal LD50

Up to and including 200 mg/kg

200–2,000 mg/kg

2,000–20,000 mg/kg

>20,000 mg/kg

Eye Effects

Corrosive corneal opacity not reversible within 7 days

Corneal opacity reversible within 7 days; irritation persisting for 7 days

No corneal opacity; irritation reversible within 7 days

No irritation

Skin Effects


Severe irritation at 72 hours

Moderate irritation at 72 hours

Mild or slight irritation at 72 hours

Signal Word






2.2 Chronic toxicity

2.2.1 Chronic Toxicity

Chronic Toxicity refers to harmful effects produced by long-term, low-level exposure to chemicals. Less is known about the chronic toxicity of pesticides than is known about their acute toxicity, not because it is of less importance, but because chronic toxicity is much more complex and subtle in how it presents itself. Increased emphasis is being given to the chronic toxicity of pesticides by the U.S. Environmental Protection Agency (EPA). In the past, more emphasis was placed on acute toxicity rather than chronic. While situations resulting in acute exposure (a single large exposure) do occur, they are nearly always the result of an accident or careless handling. On the other hand, persons may be routinely exposed to small amounts of pesticides while mixing, loading, and applying pesticides or by working in felds after pesticides have been applied.

2.2.2 Chronic Toxicity Measures

There is not a standard measure like the LD50 for chronic toxicity. How chronic toxicity of chemicals is studied depends upon the adverse effect being studied. The major chronic adverse effects include:

(1) Carcinogenesis (oncogenesis)

These terms mean the production of tumors. The terms tumor, cancer, neoplasm are all used to mean an uncontrolled progressive growth of cells. In medical terminology, a cancer is considered a malignant (potentially lethal) neoplasm. Carcinogenic or oncogenic substances are substances that can cause the production of tumors. Examples are asbestos and cigarette smoke.

(2) Teratogenesis

Teratogenesis is the production of birth defects. A teratogen is anything that is capable of producing changes in the structure or function of the offspring when the embryo or fetus is exposed before birth. An example of a chemical teratogenisis the drug thalidomide that caused birth defects in children when their mothers used it during their pregnancy. Measles virus infection during pregnancy also has teratogenic effects.

(3) Mutagenesis

Mutagenesis is the production of changes in genetic structure. A mutagen is a substance that causes a genetic change. Many mutagenic substances are oncogenic meaning they also produce tumors. Many oncogenic substances are also mutagens.

(4) Reproductive toxicity

Some chemicals have effects on the fertility or reproductive rates of animals. Reproduction studies involve the administration of a substance over one or more generations (multi-generation studies) to provide information on the effects of the substance on male and female reproductive systems, including gonadal function, the oestrus cycle, mating behaviour, conception, gestation, parturition, lactation, and weaning, and the growth and development of the offspring.

(5)Neurotoxicity Studies

A neurotoxic effect is an adverse change in the structure or function of the nervous system (central or peripheral) that results from exposure to a substance. A neurotoxic effect may arise in offspring from exposure of the mother during pregnancy and lactation. Adverse changes may result from single or repeat exposure to a substance.

Tests should be designed to detect or characterise major neurobehavioural and neuropathological effects in test animals. While behavioural effects—even in the absence of morphological changes—can reflect an adverse impact on the organism, not all behavioural changes are specific to the nervous system. Therefore, any changes observed should be evaluated in conjunction with correlative histopathological, haematological or biochemical data as well as data on other types of systemic toxicity. A developmental and delayed neurotoxicity study should be considered based on all the available information. A developmental neurotoxicity study should be conducted when neurotoxicity is observed in acute or repeat dose studies. Delayed neurotoxicity studies (acute and repeat dose) are required if the substance is an organophosphorous compound.

3. GHS and Pesticide label

GHS uses hazard class and hazard category to describe the nature and severity of chemical hazards. There are currently 29 hazard classes in GHS, among which the following classes are commonly seen on pesticides.

· Flammability;

· Acute Toxicity;

· Skin Corrosion/Irritation;

· Serious Eye Damage/Eye Irritation;

· Skin/Dermal Sensitization;

It is expected that chemical classification criteria for above hazard classes will be introduced for pesticides. It shall be noted that there is no hazard class for terrestrial animals (e.g., bees, mammals) in GHS. Different authorities may consider adding extra hazard classes for terrestrial animals when adopting GHS for pesticides.

A GHS label can also be used for pesticides after slight modification. A typical GHS label for an industrial chemical includes the following basic elements:

· Product identifier: Chemical identities of a substance or hazardous ingredients in a mixture;

· Supplier identification: The name, address and telephone number of a supplier;

· Signal word: Danger or Warning;

· Hazard pictogram: conveying different types of chemical hazards;

· Hazard statements: standardized and assigned phrases that describe the hazard(s) as determined by hazard classification;

· Precautionary statements: standardized phrases that describe measures to minimize or prevent adverse effects.

With the worldwide adoption of GHS, the acute toxicity categorization of pesticides based on GHS criteria are used in the GLP toxicity studies. The criteria of GHS acute toxicity categories are given in appendix 7.