Understanding Toxicity

Most of us have heard the phrase "the dose makes the poison," attributed to Paracelsus, a 16th Century physician who is known as the father of toxicology. A more literal translation of what he actually said is, "all things are poison and nothing is without poison, only the dose permits something not to be poisonous." This means that everything we use, including pesticides, can be potentially toxic or poisonous. The key to using products safely is to understand what toxicity means and to know how to minimize exposure to toxic substances.

Acute VS. Chronic Toxicity

Toxicity of any chemical, including pesticides, is usually classified as either acute or chronic. The difference between these two terms is based on the length of time for symptoms to appear and often on the number of times test animals such as rats, rabbits, mice or guinea pigs were exposed to the chemical.
Chronic toxicity is the result of long-term exposure to a chemical. Harmful effects may appear week, months, or years after exposure, even to small doses of a substance. Chronic effects of exposure to certain pesticides may include:

Birth defects (teratogenesis) - Women exposed to certain toxic materials such as Thalidomide during pregnancy may give birth to children with birth defects. Having measles during pregnancy also has teratogenic effects.
Benign or malignant tumors (carcinogenesis or oncogenesis are terms used for the production of malignant or cancerous tumors) - Exposure to asbestos and cigarette or cigar smoke also have carcinogenic effects. Some Vietnam War era military veterans exposed to Agent Orange (2,4-D + 2,4,5-T [accidentally contaminated with dioxin]) during their service, developed cancerous tumors many years after being exposed.
Changes in genetic structure (mutagenesis) - People, either male or female, exposed to certain toxic materials may have their genes changed in ways which can cause their children to be born with birth defects many years later. Many mutagenic substances are also carcinogenic.
Effects on fertility or reproductive rates (reproductive toxicity), which can affect either males or females
Acute toxicity, on the other hand, is based on a single short-term exposure. The effects of acute pesticide poisoning (acute toxicity) are obvious within minutes or up to several hours after the exposure.

For pesticide handlers and other people who accidentally come into direct contact with pesticides, symptoms of acute toxicity depend on the pesticide itself and the type of exposure, including:

Dermal exposure (splashing on the skin) - skin irritation, itching and reddening
Oral exposure (drinking & swallowing) - nausea, muscle twitching, sweating, weakness
Inhalation exposure (breathing fumes) - coughing, burning of the throat and lungs
Ocular exposure (splashing in the eyes) - temporary or permanent irritation or blindness

Lethal Dose 50 (LD₅₀) And Lethal Concentration 50 (LC₅₀)

LD₅₀ or Lethal Dose 50 is the term that is most often used to describe acute toxicity of any chemical, including pesticides. It is based on the amount (dose) of the chemical given at a single time which kills 50% of laboratory test animals. For pesticides, LD₅₀ values are given for oral and dermal exposure. They are usually listed as (mg/kg), which stands for milligrams of chemical per kilogram of body weight. (Mg/kg is numerically equivalent to parts per million, often abbreviated ppm.) The lower the LD₅₀, the more acutely toxic the chemical is since it only takes a small amount to kill half the test population. Thus a pesticide such as the no longer registered insecticide aldicarb which has an acute oral LD₅₀ (rabbit) of 5.3 mg/kg is much more toxic than the herbicide glyphosate which has an acute oral LD50 (rat) of >5,000 mg/kg. Remember, the lower the LD50, the more toxic the chemical.

LC50 or Lethal Concentration 50 is similar to LD₅₀, but is used for the amount of chemical in the air. LC₅₀ values are expressed in mg/l (milligrams per liter of air). Acute inhalation studies, usually lasting for 4 hours, are used to determine the concentration of a chemical which will kill 50% of laboratory test animals. In some cases, such as environmental studies which might involve test animals such as fish or aquatic invertebrates, LC₅₀ is used for the concentration of a chemical in water. In this case, it is expressed in mg/l (milligrams per liter of water).

Signal Words

The EPA has divided acute toxicity into four categories, with Toxicity Category I used for the most toxic chemicals and Toxicity Category IV used for the least toxic chemicals. Signal words are directly related to these toxicity categories, expressed as either LD₅₀ or LC₅₀ values. The charts below show this relationship.

Toxicity Category

Routes of exposure	I	II	III	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

Toxicity Category

Routes Of Exposure	I	II	III	IV
Skin Effects	Corrosive	Severe irritation at 72 hours	Moderate irritation at 72 hours	Mild or slight irritation at 72 hours
SIGNAL WORD	DANGER POISON	WARNING	CAUTION	CAUTION

From Potential Health Effects of Pesticides, The Pennsylvania State University (CODE # UO198). Adapted from 40 CFR Part 156.

Highly toxic pesticides must have the signal word of Danger/Peligro and the word Poison plus the skull and crossbones symbol printed on their containers. Pesticide handlers must be extremely careful when using these products and should be sure to use all the Personal Protective Equipment listed on the label.

The one case where the signal word is different from those listed in the table above is for pesticides which cause severe skin and eye irritation, but would have a signal word of warning or caution based on acute oral toxicity. These pesticides use the signal word of Danger / Peligro without the word poison or the skull and crossbones. This does not give any indication of acute oral toxicity.
Pesticides that are moderately toxic have the signal word of Warning / Aviso. Two to three teaspoonsful of undiluted product can kill a 150 pound person.

The least toxic pesticides have the signal word Caution. Despite some urban legends, these pesticides are not safe enough to drink.
Acute dermal toxicity, rather than acute oral toxicity, is used to determine Restricted Entry Intervals under the Federal Worker Protection Standard. Thus a pesticide such as copper hydroxide can have a high oral LD50 which gives the product a signal word of Caution, yet the REI is 48 hours because of eye and skin irritation.

Understanding Doses

Now that we have a better understanding of acute toxicity and its relationship to signal words, it is useful to have practical guidelines for doses that pesticide handlers may encounter. The USEPA uses a 150 pound (68 kg) person as "average." The chart below gives doses that could kill someone who weighs 150 pounds.

Toxicity Category	Signal Word	Oral LD ₅₀ (mg/kg)	Approximate Adult Lethal Dose (oral)
I-Highly Toxic	Danger Poison	0-50	Few drops to 1 teaspoon (tsp)
II-Moderately Toxic	Warning	51-500	1 to 3 teaspoons (3 tsp=1 Tablespoon [Tbsp])
III-Slightly Toxic	Caution	501-5,000	1 ounce (2 Tbsp) to 1 pint
IV-Relatively nontoxic	Caution	>5,000	1 pint or more

Where To Find First Aid Information

Both the pesticide label and the Material Safety Data Sheet (MSDS) are good sources for first aid information. First aid information on a pesticide label may include specific information for oral, dermal, inhalation and ocular (eye) exposure. Similar information is also found in Section 4 of the MSDS. Section 11 of the MSDS is where LD₅₀and LC₅₀ values can be found. Examples of first aid information from both the label and the MSDS of 3 pesticides is found below. It is followed by toxicological information from the MSDS of these same 3 pesticides.

Toxicity Category I - Label Excerpt ACTIVE INGREDIENT: Aldicarb 15%
SIGNAL WORD: DANGER/PELIGRO + Poison + skull and crossbones

First Aid

IF SWALLOWED:	- Immediately call a poison control center or doctor for treatment advice. - Do not induce vomiting unless told to do so by a poison control center or doctor. - Have person sip a glass of water if able to swallow. - Do not give anything by mouth to an unconscious person.
IF IN EYES:	- Hold eye open and rise slowly and gently with water for 15-20 minutes. - Remove contact lenses, if present, after the first 5 minutes, then continue rinsing. - Call a poison control center or doctor for treatment advice.
IF ON SKIN OR CLOTHING	- Take off contaminated clothing. - Rinse skin immediately with plenty of water for 15-20 minutes. - Call a poison control center or doctor for treatment advice.
IF INHALED	- Move person to fresh air. - If person is not breathing, call 911 or an ambulance, then give artificial respiration, preferably mouth-to-mouth if possible. - Call a poison control center or doctor for treatment advice.

Toxicity Category I - MSDS Excerpt, First Aid Measures: Aldicarb - 15%

SECTION 4. FIRST AID MEASURES

General	When possible, have the product container or label with you when calling a poison control center or doctor or going for treatment
Eye	Rinse immediately with plenty of water, also under the eyelids, for at least 15 minutes. Remove contact lenses, if present, after the first 5 minutes, then continue rinsing eye. Call a physician or poison control immediately.
Skin	Take off contaminated clothing and shoes immediately. Wash off immediately with plenty of water for at least 15 minutes. Call a physician or poison control immediately.
Ingestion	Call a physician or poison control immediately. Rinse our mouth and give water in small sips to drink. DO NOT induce vomiting unless directed to do so by a physician or poison control center. Never give anything by mouth to an unconscious person. Do not leave victim unattended.
Inhalation	Move to fresh air. If person is not breathing, call 911 or an ambulance, then give artificial respiration, mouth-to-mouth, if possible. Call a physician or poison control immediately.

Toxicity Category II - Label Excerpt ACTIVE INGREDIENT: Chlorpyrifos - 44.9%
SIGNAL WORD: WARNING/AVISO

FIRST AID

IF SWALLOWED:	- Immediately call a poison control center or doctor for treatment advice. - Do not induce vomiting unless told to do so by a poison control center or doctor. - Do not give any liquid to the person. - Do not give anything by mouth to an unconscious person.
IF IN EYES:	- Hold eye open and rise slowly and gently with water for 15-20 minutes. - Remove contact lenses, if present, after the first 5 minutes, then continue rinsing. - Call a poison control center or doctor for treatment advice.
IF ON SKIN OR CLOTHING:	- Take off contaminated clothing. - Rinse skin immediately with plenty of water for 15-20 minutes. - Call a poison control center or doctor for treatment advice.

Toxicity Category II - MSDS Excerpt, First Aid Measures: Chlorpyrifos - 44.9%

SECTION 4. FIRST AID MEASURES

Eye	Hold eyes open and rinse slowly and gently with of water for 15-20 minutes. Remove contact lenses, if present, after the first 5 minutes, then continue rinsing eye. Call a physician or poison control immediately.
Skin	Take off contaminated clothing. Rinse skin immediately with plenty of water for 15-20 minutes. Call a physician or poison control for treatment advice.
Ingestion	Immediately call a poison control center or doctor. Do not induce vomiting unless directed to do so by a physician or poison control center. Do not give any liquid to the person. Do not give anything by mouth to an unconscious person.
Inhalation	Move person to fresh air. If person is not breathing, call an emergency responder or ambulance, and then give artificial respiration; if by mouth-to-mouth, use rescuer protection (pocket mask, etc.). Call a physician or poison control center for treatment advice. If breathing is difficult, oxygen should be administered by qualified personnel.

Toxicity Category III - Label Excerpt ACTIVE INGREDIENT: Diquat dibromide - 37.3%

SIGNAL WORD: CAUTION

FIRST AID

IF INHALED:	- Move person to fresh air. - If person is not breathing, call 911 or an ambulance, then give artificial respiration, preferably by mouth-to-mouth, if possible. Call a poison control center or doctor for further treatment advice.
IF SWALLOWED:	- Call a poison control center or doctor immediately for treatment advice. - Have person sip a glass of water if able to swallow. - Do not induce vomiting unless told to do so by a poison control center or doctor. - Do not give anything by mouth to an unconscious person.
IF IN EYES:	- Hold eye open and rise slowly and gently with water for 15-20 minutes. - Remove contact lenses, if present, after the first 5 minutes, then continue rinsing. - Call a poison control center or doctor for treatment advice.
IF ON SKIN OR CLOTHING:	- Take off contaminated clothing. - Rinse skin immediately with plenty of water for 15-20 minutes. - Call a poison control center or doctor for treatment advice.

Toxicity Category III - MSDS Excerpt, First Aid Measures: Diquat dibromide - 37.3%

SECTION 4. FIRST AID MEASURES

Eye	If in eyes: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if present, after the first 5 minutes, then continue rinsing eye. Call the manufacturer, a physician or poison control for treatment advice.
Skin	If on skin or clothing. Take off contaminated clothing. Rinse skin immediately with plenty of water for 15-20 minutes. Call the manufacturer, a physician or poison control for treatment advice.
Ingestion	If swallowed: Call the manufacturer, a physician or poison control immediately for treatment advice. Have the person sip a glass of water if able to swallow. Do not induce vomiting unless directed to do so by the manufacturer, a physician or poison control center. Never give anything by mouth to an unconscious person.
Inhalation	If inhaled: Move person to fresh air. If person is not breathing, call 911 or an ambulance, then give artificial respiration, mouth-to-mouth, if possible. Call the manufacturer, a physician or poison control for treatment advice.

Toxicity Category I - MSDS Excerpt, Toxicological Information: Aldicarb - 15%

SECTION 11. TOXICOLOGICAL INFORMATION

Acute Oral Toxicity	Rabbit: LD50: 8.4 mg/kg
Acute Dermal Toxicity	Male rabbit: LD50: 1,960 mg/kg Female rabbit: LD50: 2,000 mg/kg
Skin Irritation	Product is highly toxic and is rapidly absorbed through the eyes and skin.
Eye Irritation	Product is highly toxic and is rapidly absorbed through the eyes and skin.
Chronic Toxicity	Aldicarb caused cholinesterase inhibition in chronic studies and rats and dogs.

Toxicity Category II - MSDS Excerpt, Toxicological Information: Chlorpyrifos - 44.9%

SECTION 11. TOXICOLOGICAL INFORMATION

Eye Irritation	May cause moderate eye irritation. May cause corneal injury. Vapors may cause eye irritation experienced as mild discomfort or redness.
Dermal	Prolonged contact may cause moderate skin irritation and redness. LD50 for a similar material for skin absorption in rabbits was >5,000 mg/kg
Ingestion	Moderately toxic if swallowed. The oral LD50 for a similar material for rats was 776 mg/kg (males) and 300 mg/kg (females). Small amounts swallowed incidentally as a result of normal handling operations are not likely to cause injury; however, swallowing larger amounts may cause injury, even death.
Inhalation	The aerosol LC50 for a similar material for rats is 2.7 mg/L for 4 hours.
Systemic	Excessive exposure may produce organophosphate-type cholinesterase inhibition.

Toxicity Category III - MSDS Excerpt, Toxicological Information: Diquat dibromide - 37.3%

SECTION 11. TOXICOLOGICAL INFORMATION

Ingestion	Oral (LD50 Female Rat): 886 mg/kg body weight
Dermal	Dermal (LD50 Rabbit): >5,050 mg/k body weight
Inhalation	Inhalation (LC50 Rat): 0.62 mg/l air - 4 hours
Eye Contact	Mildly Irritating (Rabbit)
Skin Contact	Slightly Irritant
Skin Sensitization	Not a Sensitizer (Guinea Pig)

Conclusion

Although some pesticides may have high acute oral toxicity, people who use pesticides can avoid poisoning by following label directions, especially for Personal Protective Equipment. More detailed information can be found in the MSDS for the pesticide. Remember, the lower the LD₅₀ or LC₅₀, the more toxic the chemical.

There's much to know about how to effectively and safely use pesticides.