CORE Part 1

Toxicity of Pesticides

IFAS Publication: PI-13

Prepared By: O. Norman Nesheim, Fredrick M. Fishel

and Mark Mossler

Learning Objectives:

To be more aware of the nature of toxicity

To be better able to recognize the hazards of using pesticides
To better understand how toxicity is determined
 Publication PI-13
Toxicity of Pesticides
O. Norman Nesheim, Frederick M. Fishel, and Mark Mossler

This document describes how pesticides work on living things, so you can learn to
reduce or eliminate human exposure.

Background

Pesticides are designed to control pests, but they can also be toxic (poisonous) to
desirable plants and animals, including humans. Some pesticides are so highly toxic
that very small quantities can kill a person, and almost any pesticide can make people ill
if they are exposed to a sufficient amount. Because even fairly safe pesticides can
irritate the skin, eyes, nose, or mouth, it is a good idea to understand how pesticides
can be toxic so you can follow practices designed to reduce or eliminate your exposure
and the exposure of others to them.

How Pesticides Enter the Body

Before a pesticide can harm you, it must be taken into the body. Pesticides can enter
the body orally (through the mouth and digestive system); dermally (through the skin) or
by inhalation (through the nose and respiratory system).

Oral Exposure

Oral exposure may occur because of an accident, but is more likely to occur as the
result of carelessness, such as blowing out a plugged nozzle with your mouth, smoking
or eating without washing your hands after using a pesticide, splashing concentrate
while mixing, or eating fruit that has been recently sprayed with a pesticide containing
residues above the tolerance set for the commodity by the Environmental Protection
Agency. The seriousness of the exposure depends upon the oral toxicity of the material
and the amount swallowed.

Dermal Exposure

Dermal (skin) exposure accounts for about 90% of the exposure pesticide users receive
from nonfumigant pesticides. It may occur any time a pesticide is mixed, applied, or
handled, and it often goes undetected. Both liquid pesticides and dry materialsdusts,
wettable powders, and granulescan be absorbed through the skin.

The seriousness of dermal exposure depends upon:

the dermal toxicity of the pesticide;

rate of absorption through the skin;
 the size of the skin area contaminated;
the length of time the material is in contact with the skin; and
the amount of pesticide on the skin.

Absorption continues to take place on all of the affected skin area as long as the
pesticide is in contact with the skin. The seriousness of the exposure is increased if the
contaminated area is large or if the material remains on the skin for a period of time.

Rates of absorption through the skin are different for different parts of the body. Usually,
absorption through the forearm is the standard against which absorption rates in other
areas of the body is tested. Absorption is over 11 times faster in the lower groin area
than on the forearm (Table 1). Absorption through the skin in the genital area is rapid
enough to approximate the effect of injecting the pesticide directly into the bloodstream.

Table 1. Parathion absorption rates through the skin on various bodily regions .
Body region Percent relative absorption
Forearm 8.6
Palm of hands 11.8
Ball of foot 13.5
Abdomen 18.4
Scalp 32.1
Forehead 36.3
Ear canal 46.5
Genitalia 100

Inhalation Exposure

Inhalation exposure results from breathing pesticide vapors, dust, or spray particles.
Like oral and dermal exposure, inhalation exposure is more serious with some
pesticides than with others, particularly fumigant pesticides, which form gases.

Inhalation exposure can occur by breathing smoke from burning containers; breathing
fumes from pesticides while applying them without protective equipment; and inhaling
fumes while mixing and pouring pesticides. Some pesticides will have statements on
their labels requiring the use of a specified respirator. Another means of inhalation
exposure is smoking tobacco products containing pesticide residues.

Toxicity

Toxicity refers to the ability of a substance to produce adverse effects. These adverse
effects may range from slight symptoms such as headaches to severe symptoms like
coma, convulsions, or death. Poisons work by altering normal body functions. Most toxic
effects are naturally reversible and do not cause permanent damage if prompt medical
treatment is sought. Some poisons, however, cause irreversible (permanent) damage.
 Toxicity is usually divided into two types, acute or chronic, based on the number of
exposures to a poison and the time it takes for toxic symptoms to develop. Acute toxicity
is due to short-term exposure and happens within a relatively short period of time,
whereas chronic exposure is due to repeated or long-term exposure and happens over
a longer period. (Table 2).

Table 2. Types of toxicity.

Time for symptoms
Type Number of Exposures
to develop
Acute usually 1 immediate (minutes to hours)
Chronic more than a few one week to years

How Toxicity Is Measured

All new pesticides are tested to establish the type of toxicity and the dose necessary to
produce a measurable toxic reaction. In order to compare the results of toxicity tests
done in different labs, there are strict testing procedures. Toxicity testing is extensive
(involving many phases) and therefore expensive. Humans, obviously, cannot be used
as test subjects, so toxicity testing is done with animals and plants. Since different
species of animals respond differently to chemicals, a new chemical is generally tested
in mice, rats, rabbits, and dogs. The results of these toxicity tests are used to predict the
safety of the new chemical to humans.

Toxicity tests are based on two premises. The first premise is that information about
toxicity in animals can be used to predict toxicity in humans. Years of experience have
shown that toxicity data obtained from a number of animal species can be useful in
predicting human toxicity, while data obtained from a single species may be inaccurate.
The second premise is that by exposing animals to large doses of a chemical for short
periods of time, we can predict human toxicity from exposure to small doses for long
periods of time. Both premises have been questioned.

Chronic toxicity is tested using animal feeding studies. In these studies, the pesticide
under investigation is incorporated into the daily diet and fed to animals from a very
young to a very old age. These, as well as the reproductive effects studies, are
designed to arrive at a No-Observable-Effect-Level (NOEL); that is, a level in the total
diet that causes no adverse effect in treated animals when compared to untreated
animals maintained under identical conditions. This NOEL is expressed on a mg/kg of
body weight/day basis.

A Reference Dose (RfD), also known as Acceptable Daily Intake (ADD), is usually
established at 1/100 of the NOEL, in order to add an additional margin of safety. The
RfD (ADI) is the amount of chemical that can be consumed daily for a lifetime without ill
effects.
 Acute Toxicity

The acute toxicity of a chemical refers to its ability to do systemic damage as a result of
a one-time exposure to relatively large amounts of the chemical. A pesticide with a high
acute toxicity may be deadly if even a very small amount is absorbed. The signal words
on the label (Table 3) are based on the acute toxicity of the pesticide. Acute toxicity may
be measured as acute oral (through the mouth), acute dermal (through the skin) and
acute inhalation (through the lungs or respiratory system).

Table 3. Acute toxicity measures and warnings.

Categories of Acute Toxicity
LD50 LD50 LC50
Oral Dermal Inhale
Categories Signal Word Oral Lethal Dose1
mg/kg mg/kg mg/l
DANGER, POISON (skull & a few drops to a
I Highly Toxic 0 to 50 0 to 200 0 to 0.2
crossbones) teaspoonful
II Moderately over a teaspoonful to
WARNING 50 to 500 200 to 2,000 0.2 to 2.0
Toxic one ounce
500 to 2,000 to over one ounce to one
III Slightly Toxic CAUTION 2.0 to 20
5,000 20,000 pint
IV Relatively Non- over one pint to one
CAUTION (or no signal word) 5,000+ 20,000 + 20 +
toxic pound
1
Probable for a 150 lb.-person.

Acute Toxicity Measures

The commonly used term to describe acute toxicity is LD 50. LD means lethal
dose (deadly amount) and the subscript 50 means that the dose was acutely lethal to
50% of the animals to whom the chemical was administered under controlled laboratory
conditions. The test animals are given specific amounts of the chemical in either one
oral dose or by a single injection, and are then observed for a specified time.

The lower the LD50 value, the more acutely toxic the pesticide. Therefore, a pesticide
with an oral LD50 of 500 mg/kg would be much less toxic than a pesticide with an LD 50 of
5 mg/kg. LD50 values are expressed as milligrams per kilogram (mg/kg), which means
milligrams of chemical per kilogram of body weight of the animal. Milligram (mg)
and kilogram (kg) are metric units of weight. Milligrams per kilogram is the same
measure as parts per million. To put these units into perspective, 1 ppm is analogous to
1 inch in 16 miles or 1 minute in 2 years.

For example, if the oral LD50 of the insecticide parathion is 4 mg/kg, a dose of 4 parts of
parathion for every million parts of body weight would be lethal to at least half of the test
animals.

LD50 values are generally expressed on the basis of active ingredient. If a commercial
product is formulated to contain 50 percent active ingredient, it would take two parts of
the material to make one part of the active ingredient. In some cases, other chemicals
mixed with the active ingredient for formulating the pesticide product may cause the
toxicity to differ from that of the active ingredient alone.

Acute inhalation toxicity is measured by LC50. LC means lethal concentration.

Concentration is used instead of dose because the amount of pesticide inhaled in the
air is being measured. LC50 values are measured in milligrams per liter. Liters are metric
units of volume similar to a quart. The lower the LC50 value, the more poisonous the
pesticide.

Chronic Toxicity

Chronic toxicity refers to harmful effects produced by long-term exposure to pesticides.

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 gradual
rather than immediate and is revealed in much more complex and subtle ways. 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 pesticides while mixing, loading, and applying pesticides or
by working in fields after pesticides have been applied.

Chronic Toxicity Measures

There is no standard measure like the LD50 for chronic toxicity. How chronic toxicity of
chemicals is studied depends upon the adverse effect being studied. Chronic adverse
effects may include carcinogenic effects (cancers), teratogenic effects (birth defects),
mutagenic effects (genetic mutations), hemotoxic effects (blood disorders), endocrine
disruption (hormonal problems), and reproductive toxicity (infertility or sterility).

Carcinogenesis (oncogenesis)

Carcinogenesis means the production of malignant tumors. Oncogenesis is a generic

term meaning the production of tumors which may or may not be carcinogenic. The
terms tumor, cancer, or 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.

Teratogenesis

Teratogenesis is the production of birth defects. A teratogen is anything that is capable

of producing changes in the structure or function of an embryo or fetus exposed before
birth. An example of a chemical teratogen is the drug thalidomide, which caused birth
defects in children when their mothers used it during their pregnancies. Measles virus
infection during pregnancy has teratogenic effects.
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.

Reproductive toxicity

Some chemicals have effects on the fertility or reproductive rates of animals. Males or
females can be affected.

Label Identification of Acute and Chronic Toxicity

To alert pesticide users to the acute toxicity of a pesticide, a signal word may appear on
the label. Four different categories are used (Table 3). Signal words are used to tell the
user whether the chemical is highly toxic, moderately toxic, slightly toxic, or relatively
non-toxic. These label warnings are based, for the most part, on the chemical's acute
toxicity. For example, the acute oral and acute dermal toxicity of a pesticide may be in
the slightly toxic category. But if the acute inhalation toxicity is in the highly toxic
category, the pesticide label will have the signal words for a highly toxic pesticide. The
degree of eye or skin irritation caused by the pesticide also influences the signal word.

For chronic toxicity there is no comparable set of signal words like those used for acute
toxicity. Instead, a statement identifying the specific chronic toxicity problem is
sometimes used on the label. Such a statement might read "This product contains
(name of chemical), which has been determined to cause tumors or birth defects in
laboratory animals." Chronic toxicity warning statements may be accompanied by label
directions to wear certain kinds of protective clothing when handling or working with the
pesticide to minimize or eliminate exposure to the pesticide.

It is important to read the label to look for signal words identifying the product's acute
toxicity and for statements identifying any chronic toxicity problem. A pesticide may be
low in acute toxicity (signal word caution), but it may have a label statement identifying
potential chronic toxicity.

Safety Factors

Extensive residue trials are conducted on crops to determine levels of the pesticide that
remain in or on growing crops after treatment with the pesticide. These trials lead to the
establishment of a tolerance for residues of the chemical on food commodities. A
tolerance is the maximum allowable amount of the pesticide permitted in or on a specific
food commodity at harvest. The directions for use found on the product label are written
to assure that residues in food commodities are below the tolerance. The tolerance is
set low enough to assure that even if someone ate only food items with residues of a
given pesticide at the tolerance limit, there would still be a safety factor of at least 100
when compared to a level causing no observable effects in laboratory animals. This is,
of course, a worst-case situation, since all crops on which the pesticide is registered for
use would not be treated with the chemical, and in most cases residue levels would be
well below the tolerance because pre-harvest intervals are almost invariably longer than
the minimum period stated on the label. Further reduction of residues may occur in
storage or from washing, trimming, and processing.

Dose-response

Dose-response is the measure of the amount of a given substance an organism must

absorb to produce an effect. The extensive amount of data developed about a given
pesticide is often used against it because this key piece of information is ignored. For
example, some acute toxicity studies, which are designed to include dosage levels high
enough to produce deaths, are cited as proof of the chemical's dangers. Chronic effects
seen at very high doses in lifetime feeding studies are misinterpreted and considered as
proof that no exposure to the chemical should be allowed.

Major improvements in analytical chemistry permit detection of the presence of

chemicals at extremely low levels of parts per billion (ppb) and even sometimes parts
per trillion (ppt). A certain chemical may have been found in a food or beverage, and the
amount found is expressed in parts per million or parts per billion. Often, no information
is provided to assist consumers in comprehending the meaning of these numbers.
Frequently, this information neglects the issue of dose-response, the key principle of
toxicology, which, simply stated, is "the dose makes the poison." The concentration of a
chemical in any substance is meaningless unless it is related to the toxicity of the
chemical and the potential for exposure and absorption. Chemicals of low toxicity such
as table salt or ethyl alcohol can be fatal if consumed in large amounts. Conversely a
highly toxic material may pose no hazard when exposure is minimal.

Monitoring for Residues

Monitoring foods for pesticide residues is carried out by the Food and Drug
Administration (FDA) and the United States Department of Agriculture (USDA). Crops
found to contain residues over the official tolerance (maximum legal level) established
by the EPA must be destroyed. The threat of crop destruction with resultant financial
loss is a strong incentive for farmers to observe use instructions on pesticide labels and
thus assures that residues will be below established tolerances. Crops grown for export
are often checked for residues by foreign residue laboratories to assure that local
tolerance limits are not exceeded. Lastly, market-basket surveys (analyses of food
items from grocery stores) have confirmed the low exposure of the general public to
pesticides in foods.

Hazard

Hazard is a function of the toxicity of a pesticide and the potential for exposure to it. We
do not have control of the toxicity of a pesticide because toxicity is a given characteristic
of a particular pesticide; however, we can have control over our exposure to pesticides.
We achieve control over exposure by following several safety practices including the
use of protective clothing and equipment (PPE).

All pesticides are hazardous if misused, no matter what their toxicity. All pesticides can
be handled safely by using safety practices that minimize or eliminate exposure to them.

Federal laws regulating pesticides have placed the burden of proving safety of pesticide
usage on the manufacturer. Hazard evaluation studies are generally done by scientific
laboratories maintained by the manufacturer or through outside contract laboratories.
Few products are subjected to the extensive and vigorous testing pesticides undergo
before they are marketed. In fact, many promising pesticide products are not marketed
because they do not pass the extensive toxicology testing. Older pesticide products that
were registered before the current toxicology testing standards were established are
being re-evaluated to ensure they meet current standards. Precautions and other safety
information found on the product's label are based on information from these tests. By
reading and following the directions on the label, users can minimize or eliminate
hazards due to use of the pesticide to themselves and others.

Common Pesticide Poisonings

The pesticides most often implicated in poisonings, injuries, and illnesses, according to
2010 data from the American Association of Poison Control Center's Toxic Exposure
Surveillance System, are listed in Table 4.

Cases listed as organophosphates (and the other categories as well) may also include
other insecticides such as carbamates and organochlorine in a single product.
Asymptomatic cases are included in Table 4 only.

This list can't be considered representative of all symptomatic poisonings because it

only shows cases reported to Poison Control Centers. However, it does give a sense of
the relative frequency and risk of poisoning from various agents or classes of agents.
The relative frequency of cases generally reflects how widely a product is used in the
environment. For example, a number of disinfectants occur in the top ten partly because
they are far more commonly found in the home and work environment than other
pesticides. Denominator information on the population at risk (numbers exposed) would
be needed to better understand the relative risk of different pesticides. However, the
main purpose is to give physicians a sense of what types of cases they are most likely
to see in their practice.
 Table 4. Pesticide exposures most commonly reported to National Poison Data System
(2010) http://www.aapcc.org/data-system/.

Child <5 612 1319 >20 Unknown

Rank Pesticide or pesticide class Total
years years years years age
1 Pyrethrins and pyrethroids 7,717 1,672 1,222 14,800 2,706 28,117
2 Disinfectants 12,018 1,182 1,270 7,906 1,892 24,268
3 Rodenticides 10,961 293 162 1,046 408 12,870
4 Insect repellents 6,372 1,013 381 2,272 680 10,718
5 Herbicides 2,019 362 246 4,593 817 8,037
6 Borates and boric acids 4,270 92 62 466 110 5,000
7 Organophosphates 880 218 156 1,826 404 3,484
8 Carbamates 804 119 83 1,027 221 2,254
9 Fungicides 171 25 21 414 73 704
10 Organochlorines 182 30 15 245 58 530
11 Fumigants 48 19 14 213 56 350
All other insecticides (including
5,526 615 387 5,264 1,371 13,163
unknown)
Total pesticides/disinfectants 50,968 5,640 4,019 40,072 8,796 109,495