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Hazard, risk, human health and pesticides

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Assessing the risk to human health: How is the risk (associated with using a pesticide) to human health assessed?

There are five stages of risk assessment for human health:

  1. Toxicological hazard assessment
  2. Dose-response evaluation
  3. Human exposure assessment
  4. Risk characterisation
  5. Risk management

For a risk to occur there must be exposure to a hazard. Risks can be minimised once the hazard and the routes of exposure to the hazard are understood. In virtually all countries therefore, pesticides must undergo a rigorous regulatory procedure designed to determine the hazard level of a product and assess the risks associated with that product before gaining approval and being placed on the market. Applicants must provide an extensive data package of studies complying with international guidelines (eg OECD Guidelines ).

Data provided includes information about the:

  • Physical and chemical properties (physical aspects – eg solid/liquid or gas, its boiling point, colour, pH and so on; and how it reacts with other substances;
  • Ecotoxicology (how the substance effects living organisms);
  • Environmental chemistry and fate (how the substance behaves in the environment);
  • Biological efficacy (showing the product works for its intended purpose, eg to control particular pests);
  • Residues in treated crops (determining the levels of the pesticide remaining in harvested produce after treatment with the pesticide);
  • Crop and animal metabolism (understanding what happens to the pesticide once inside plants and animals);
  • Toxicology (understanding the effects on human health, based on standard animal tests).

All this data is used as the basis for establishing the hazard profile (i.e. a description of all the hazards associated with that substance) and conducting risk assessments.

Risk Assessment Stage 1: Toxicological Hazard Assessment

Toxicological hazard assessment is the identification of intrinsic toxicological properties of a substance. The toxicological properties are investigated by conducting a set of internationally approved animal (normally rat and another animal) studies. For pesticides, the toxicological studies that are conducted include:

  • Acute toxicity (a range of tests to assess what happens after a single dose is administered or within 24 hours of exposure i.e. eye irritation, skin irritation, skin sensitisation, acute oral toxicity, acute dermal toxicity and acute inhalation toxicity);
  • Sub chronic toxicity (short-term studies where repeated doses are administered from 28 days to 90 days and various toxic effects in the body such as abnormalities in the blood and in the liver are examined);
  • Chronic toxicity (long-term studies where repeated doses are administered for  up to 2 years, looking at long-term effects such as cancer, effects on the developing foetus, organ disease and effects on reproduction);
  • Special studies as required, eg neurotoxicity (studying effects on the nervous system);
  • Metabolism, distribution and excretion (how the pesticide is broken down in the body and excreted).

WHO hazard classification based on LD50

The WHO hazard classification system uses the acute and dermal LD50 in rats to classify pesticides into five groups ranging from “extremely hazardous” to “unlikely to present a hazard in normal use”. The LD50 is the amount of substance that causes one half of the animals in a toxicological test to die, i.e. it is the measure of the lethal dose to 50% of the animals treated. This is one of the most commonly used measures (endpoints) of relative toxicity.

All substances theoretically have an LD50, and thousands of common substances (including food ingredients) and chemicals have been tested. The lower the LD50 the more toxic the substance is taken to be, because it means a relatively smaller dose gives the same toxic effect (in this case death) if exposure occurs. Examples of some LD50s for various substances are shown below.

LD50: mg/kg bw  



Botulinum Toxin A (causes botulism food poisoning)



Strychnine (animal bait)


Hydrogen cyanide (industrial chemical)


Parathion (insecticide)


Brodifacoum (rat bait)


Sodium flouride (added to drinking water, toothpaste)


Nicotine (stimulant in tobacco)


Endosulfan (insecticide)


Phenobarbitol (barbituate)


Caffeine (in coffee, cola etc)


Paraquat dichloride (herbicide)


Ammonia (used in industry and in  household cleaners)


Aspirin (analgesic)


Sodium chloride (table salt)


Glyphosate (herbicide)

 The LD50 is a tool that can be used to compare toxicity of substances but it is not the measure of risk

The classification is then used to produce the product label warning information, which alerts users to the potential toxicity of the pesticide.

Table showing the type of warning information to appear on pesticide label by hazard class (46 Kb JPEG)
Table showing the type of warning information to appear on pesticide label by hazard class.

Pesticides which are classified as extremely hazardous generally need to be used with a great deal more caution and protective equipment than those that are classified as unlikely to present a hazard.

Example of WHO hazard classification symbol on a pesticide product label (43 Kb JPEG)
Example of WHO hazard classification symbols on a pesticide label

The WHO hazard classification system is being replaced in many countries by the GHS classification system – the Globally Harmonised System for Classification and Labelling of Chemicals. The GHS system uses different toxicity levels and effects than the WHO system, and also uses different pictograms and warning statements.

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Risk Assessment Stage 2: Dose Response Evaluation

The dose response evaluation 

  • measures the toxic effects in the body relative to dose administered and is more formally defined as:
  • the determination of the quantitative relationships between internal dose and effects observed.

The approach most commonly used for pesticides is to find the dose below which no toxicologically significant effect occurs i.e. the ‘No Observed Adverse Effect Level’ (NOAEL). To find the NOAEL for a particular product, the NOAEL is found for each of the short-term and chronic studies conducted as part of the toxicological hazard assessment. A similar term, ‘No Observed Effect Level’ (NOEL) is also used.

The diagram below shows a dose response curve for a typical substance, e.g. Chemical A, and plots increasing dose versus increasing effect. The NOAEL is set just below the point where the dose response curve crosses the vertical toxic line. It is in fact a threshold between no toxic effects and toxic effects. Using wine as an example, many people can drink one glass of wine with no observable effects but two glasses might start to give observable effects such as mood change, light-headedness, flushed face and quickening pulse rate. Thus, in this example one glass of wine would be the No Observed Adverse Effect Level, because above this level effects start to occur.

Diagram illustrating dose response curve for Chemical A (9 Kb GIF)
Diagram illustrating dose response curve for Chemical A

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Risk Assessment Stage 3: Human Exposure Assessment

The toxicological hazard assessment and the dose response evaluation looked at data from animal studies. The human exposure assessment stage examines how this data relates to humans, in particular in relation to real exposure situations. So for pesticides, we need to look at the people who are using them – the spray operators - by means of exposure modelling and personal monitoring and also conduct dietary risk assessments for consumers.

Exposure modelling: Calculations are done on all the real-life situations of use where users may be exposed, e.g.

  • mixing up the dilute spray, 
  • loading it into the spray tank, 
  • performing the actual spraying on specific crops,
  • re-entering into the field, 
  • cleaning up the sprayer,
  • disposing of the left-over spray and empty packaging.

How often a person is likely to use the product and for what length of time they will spray each day is also factored in.

The total amount of exposure from all these situations is then put into an exposure model which calculates the dose estimated to be received and the estimated dose is compared to the threshold dose. The Acceptable Dose in Humans (or acceptable daily intake) is calculated from the no observed adverse effects level - NOAEL (which is the output of the dose response evaluation stage) ; there is usually a minimum 100 fold margin of safety from the NOAEL incorporated into the Acceptable Dose in Humans; 10 fold for inter-species variation and 10 fold for intra-species variation.  This translates into an extremely large margin of safety. 

If the model shows that the exposure level will be higher than the Acceptable Dose in Humans, then the pesticide cannot be registered for the specific crops tested for and either the crop uses are restricted, and/or the exposure is controlled by mandating higher levels of PPE or other mitigating factors are applied.

Personal monitoring can also be conducted. This is where the pesticide is actually applied by a person in a test situation and then samples of urine or in some cases blood are taken and tested for traces of the pesticide. Skin swabs can be taken for analysis as well as expired air (the breath). The clothing is also analysed. This gives a picture of how much the person spraying has been exposed and how much is absorbed into the body (see below).  However, this is usually only necessary if the exposure modelling does not demonstrate the stringent minimal 100 fold degree of safety.

Dietary risk assessments: As pesticides are applied to food crops, minute remains of the pesticides may still be present in the harvested food at the time that the consumer eats it. These levels are very low.  Nevertheless a full evaluation of the effect on the human population must be conducted. These evaluations are called dietary risk assessments and are done in great detail, looking at exactly 

  • which crops will be sprayed,
  • how the pesticide is degraded in that crop, 
  • how much is still present at harvest, and 
  • how much people eat on average of that particular food.

This evaluation takes into account different diets, for example Europeans consume a large amount of wheat bread where as Asians consume a large amount of rice. At the end of these calculations the Acceptable Daily Intake (ADI) is determined. This is the amount of the pesticide that we can confidently predict that a person can consume over the course of their lifetime without any adverse effects.

Routes of exposure

This is basically how the pesticide gets into the body. In addition to how often and for how long exposure occurs (frequency and duration), the route of exposure is important.

Diagram showing routes of exposure; dermal exposure (through the skin), inhalation, ingestion(18 Kb JPEG)
Routes of exposure; dermal exposure (through the skin), inhalation, ingestion

For pesticides there are 3 main routes of exposure into the human body – dermal exposure, inhalation and ingestion:

  1. Dermal exposure: the chemical permeating the skin. For pesticides, the skin is the most important route of exposure, from splashes of liquid formulations or spray mixtures onto the skin, or by coming into contact with the spray. 
  2. Inhaling the chemical through the nose and mouth into the airways either by inhalation of the pesticides directly or by inhalation of the spray droplets.  Direct inhalation of a pesticide only occurs for pesticides that are volatile i.e. that evaporate into the air; the greater the volatility of a pesticide the greater the risk of inhalation. However many pesticides are practically non-volatile. Inhalation of spray droplets  occurs only very rarely since when pesticides are sprayed, the droplets are much too large to get right into the lungs and the largest droplets are trapped in the nasal passage or the mouth. These droplets would then normally be sneezed or spat out however some very small amounts may be ingested (see below). Only droplets less than 7 µm VMD can travel into the trachea or bronchi, and only extremely small droplets, less than 2 µm VMD, can reach the alveoli and hence get into the blood stream via respiration.

The typical spray contains a range of droplet sizes depending on the equipment used (eg, type of nozzle and pressure). For knapsack spraying most droplets are between 200 to 250 µm VMD although the range may be from 10 to 1000 µm VMD. In an average knapsack spray the percentage of droplets that can reach the alveoli is 0.2%. Considering that sprays are already dilute forms of pesticide, this is an insignificant amount.

In an average knapsack spray the percentage of droplets that can reach the alveoli is 0.2%. This is an insignificant amount. Diagram of inhalation (34 Kb JPEG)
In an average knapsack spray the percentage of droplets that can reach the alveoli is 0.2%. This is an insignificant amount.

The third route of exposure is:

3.  Ingesting the chemical through the mouth into the digestive tract. This rarely occurs through occupational use of pesticides when very small amounts of spray mist may enter the nose and mouth and be swallowed. As this is a potential cause of exposure however, it is essential to take protection against this happening by not walking into spray mist and by using appropriate PPE. 

What happens after exposure - absorption, distribution, metabolism and excretion

For harm to occur there needs to be exposure and absorption. Substances can have different rates or levels of absorption depending on their chemical and physical properties. A comparison of the skin absorption of some pesticides as a percentage of applied dose is shown below:


% Dose


% Dose



























Feldmann and Maiback 1974 and Wester et al 1984

It is clear that some, such as carbaryl, are very easily absorbed, whereas others, such as paraquat, have a very low absorption level. This means that if the same amount of skin exposure occurs to each, a high amount of the carbaryl will enter the body but only a minute amount of the paraquat will.

Different parts of the body have different absorption rates. This is mainly related to the thickness of the skin; the thinner the skin the more easily the chemical is absorbed and the higher the absorption rate. Conversely, the thicker the skin, the less chemical is absorbed and the lower the absorption rate.

Diagram of absorption rates of human body.(11 Kb GIF)
Areas with thicker skin can offer greater resistance to toxic substances than those areas with thinner skin

Some substances are absorbed much more readily via the digestive tract than via the skin and vice versa. And obviously gases (substances in the air) are much more likely to be absorbed through the lungs.


After absorption the way the substance behaves in the body system is also important. If absorbed into the blood stream, there is the potential for the substance to be moved around the body from the site of absorption to other organs or parts of the body. A simple example is when a lot of garlic is eaten, it is absorbed via the digestive tract into the blood where a portion of it is circulated to the lungs and expired back out in the breath (which is normally quite noticeable!). This is distribution.


After (and at times during) distribution there are a lot of other processes going on. These are grouped under the umbrella term of metabolism. Again using food as an example, the food we eat is not in the form that the body can actually use – it must be broken down into simpler components that can be moved into the various tissues and cells to provide the nutrients we need to sustain life. The same process happens for many other substances that are commonly ingested such as drugs, pharmaceuticals and pollutants in the air. The majority of toxins are also broken down this way, including pesticides.


Finally, how the substance is excreted is taken into account. Excretion is elimination from the body – via urine, faeces, through the skin (sweat) or the lungs. Many toxins or break-down products of toxins are eliminated rapidly via the urine. Some substances are excreted directly, unchanged, without going through metabolism. However other substances are not well eliminated and may even remain stored in the body. This mostly applies to fat-soluble substances, because fat is the body’s storage material, and fat-soluble substances can get trapped in the body fat.

Linking exposure and absorption to toxic effects

If exposure and absorption of pesticides occurs, this may lead to toxic effects. The degree and type of effect depends on the factors described on the page basic principles of toxicology. The toxic effects can be transitory if the body is able to overcome the effects (eg, through repairing cell damage), or the effects may be more permanent such as liver or lung damage or even death.

Diagram linking exposure and absorption to toxic effect (24 Kb JPEG)
The toxic effects can be transitory if the body is able to overcome the effects (eg, through repairing cell damage), or the effects may be more permanent such as liver or lung damage or even death.

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Risk Assessment Stage 4: Risk Characterisation

Risk characterisation is the pulling together of all the above information (toxicological data, hazard profile, exposure modelling etc ) to draw conclusions on the probability of toxic effects under conditions of use and hence decide whether the pesticide can be used safely or not.

Risk characterisation is carried out by the government regulatory authorities of different countries/or groups of countries. Since government regulatory systems have become more stringent in recent years, very toxic pesticides no longer pass the requirements and cannot be registered and sold in some countries. Only pesticides with lower toxicity are able to pass.

Different regulators use different approaches but all include a safety margin or safety factor in their risk characterisation process. This safety factor is an additional factor, normally 100x (100 times). It is put into the equation to ensure that the maximum possible exposure is always going to be less than the no observable adverse effects levelNOAEL - by at least 100 times. The safety factor is like an allowance for the uncertainty of applying results of laboratory studies with animals to real-life situations with humans. The United States Environmental Protection Agency (USEPA) uses different approaches depending on the hazard profile of the pesticide. The NOAEL approach is one of these and which in simple terms is:

Calculated SAFETY MARGIN for this pesticide in this crop = NOAEL/EXPOSURE mg/kg bw

Here the calculated safety margin for the particular pesticide and use is compared to the acceptable or allowable safety margin.

The European Union Commission uses a slightly different formula that essentially gives the same result.


Where AOEL = Acceptable Operator Exposure Level and operator refers to anyone who is using or working with the pesticide. Again a safety factor of 100 times is usually used.

Risk Management: After the risks are characterised the government regulators will nearly always set conditions of use relating to the pesticide in question, in order to manage those risks adequately.

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Risk Assessment Stage 5: Risk Management

After the risks are characterised i.e. when the risk of using a particular pesticide to human health is understood and quantified, the government regulators will nearly always set conditions of use relating to the pesticide in question. This is in order to manage those risks adequately.

Regulators place the responsibility of implementing these conditions on both the company manufacturing and supplying the pesticide and also on the person purchasing, using and storing the pesticide. For example, in most cases it is mandatory that impermeable gloves are worn whilst mixing pesticides sprays to reduce the risk of dermal exposure. This is a simple form of risk management. Examples of various risk management strategies are:

  • Product labels giving text information on:
    • Instructions for use;
    • Warnings and precautions;
    • First aid instructions; supplemented by
    • pictograms.
  • Regulatory restrictions (e.g. limits on the quantity of the pesticide that can be sprayed in a year, what crops it can be used on and what type of personal protective equipment (PPE) must be worn when using the pesticide).
  • Exposure mitigation:
    • Engineering controls (e.g. enclosed tractor cabins);
    • Personal protection measures (e.g. what type of PPE must be worn);
  • Surveillance (i.e. monitoring the health of the sprayer operators).
  • Training, education and advice from experts such as extension officers.

There may be many others, such as environmental risk management strategies.

The above information is really a simplified explanation of the steps that are carried out to ensure the safety of pesticides in use. The process itself is very complex, with thousands of pages of data to be analysed and many different risk assessments to be performed.  In the end, the purchaser or user of the pesticide can be assured, that if they use the pesticide according to the label instructions and take heed of the basic 5 Golden Rules for Safe Use, there is a large margin of safety and they should not come to any harm.

Further Information

For further detailed information on using pesticides safely, look at the other training modules in this series or seek advice from your local dealer, extension officer or industry representative.

Note to readers: This is a complicated subject which is difficult to explain. If there are sections which could be better or if you have suggestions as to how we can improve the page - please contact us



Health Protection Agency

Chemicals and Society

Assessing Health Risks from Pesticides

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Hazard, risk, human health and pesticides | Basic principles of toxicology | Assessing the risk to human health | Glossary - human health section