Toxicological assessment

Changed on: 06.05.2016

Toxicological studies are used to identify properties of pesticides and their active ingredients and metabolites that may pose a health risk. Two exposure scenarios play a role in the toxicological assessment of pesticides for which different health-related limit values are established: People may on the one hand come into contact with the pesticide and its active substances during application thereof and during subsequent work in the field via inhalation and/or skin contact. On the other hand, consumers can absorb pesticide residues via their food.

For the assessment of the risk (to the consumer) the following two limit values for exposure are calculated using the relevant toxicological studies:

1. Acceptable Daily Intake (ADI)

ADI is used as a limit value in the health risk assessments for long-term intake of active substances in pesticides via food. It defines the amount of a substance that a consumer can absorb daily and over their lifetime without any identifiable risk to health taking all available knowledge into account.

2. Acute Reference Dose (ARfD)

The acute reference dose was introduced in addition to the ADI value for those active ingredients in pesticides which have a high acute toxicity and were shown to have damaging effects to health in animal experiments even after a single or short-term intake. The acute reference dose (ARfD) defines the quantity of a substance that may be ingested via food on a daily basis with no identifiable risk to the consumer.

Feeding studies using the active substances in the feed for various types of animals form the basis for the derivation of these toxicological limit values (ADI, ARfD). Generally, a quantitative relationship is to be observed between the degree of exposure and the extent or frequency of the occurrence of an effect which is referred to as the so-called “dose-effect relationship.” Since the effect (which poses the risk to health) is a function of the dose, it is possible to ascertain the range of doses that have no impact on health by conducting experiments using several groups of animals being given varying doses. The highest dose of a substance at which there is no identifiable damaging impact is referred to as the NOAEL (No Observed Adverse Effect Level).

The NOAEL is the basis from which regulatory limit values are derived according to the NOAEL “safety factor” concept. Based on all available information the NOAEL originating from a study which corresponds to the expected pattern of exposure (single, short-term or life-long exposure) and which was conducted using the most sensitive type of animal, is chosen for the purpose of deriving a specific limit value. In order to take any possible difference in the sensitivity between man and beast but also individual differences within the human population into account a so-called “safety factor” is included in the calculation of limit values (default value 100).

In addition to the aforementioned toxicological parameters (ADI, ARfD) the determination of the type and quantity of pesticide residue is also part of the assessment:

Residue definition (Type of residue)

The degradation behaviour of active ingredients in pesticides is tested by means of metabolism studies in plants and animals. As part of this process, any metabolites (by-products of the active ingredients) are also identified. The outcome of these tests is residue definition: i.e. the form in which the active substance occurs in the harvested crop or in foodstuffs of animal origin.
Residue definition is the basis for the determination of maximum residue levels, the development of suitable analysis methods for monitoring crop products, as well as risk assessment.

Determining residue quantity in tests

The level of residues to be expected in the crop/product after the use of pesticides is determined using field studies on cultivated plants and feeding trials with agricultural livestock. In the studies the crops, for which licensing approval of the pesticide was applied for are treated with the pesticide or animals fed with feedstuff that contains the amount of residues to be expected. The influence of processing operations (for example the production of wine from treated grapes) is also investigated as part of the above.

Based on the results of the residue experiments a maximum value (Maximum Residue Level - MRL) is determined for the relevant active substance in the pesticide using statistical calculation methods.

Furthermore, the impact of processing on the type and amount of residues is also investigated. On the basis of these processing studies (e.g. grain into bread, grapes into wine, hops into beer) the so-called “processing factors” are derived that provide information as to whether additional by-products (metabolites) are formed in the processed product and/or to what extent a reduction of the residues (dilution) or a concentration of the residues (e.g. through drying) occurs.

Also, within the scope of the licensing process the situation regarding residues is assessed in crops that may be planted subsequently as part of crop rotation: it is therefore entirely possible that MRLs may be derived for crops that are not directly treated with the pesticide (absorption of residues from the soil). 
Residue behaviour of pesticides:
• Factors influencing the amount of residues
• Toxicological assessment and pesticide residues
• Risk assessment
• Maximum residue levels, MRLs