Report of the sub-committee on the environment and health.
Annex 2
The general rules for risk assessment of environmental impacts and classification of health impacts
1 Environmental impacts
1.1 Risk of persistence, mobility and bioaccumulation
With respect to properties relating to persistence, mobility and bioaccumulation, it is judged whether there is a risk of the prescribed values for whether an product can be directly accepted being exceeded in the given conditions of use. Initially, the available laboratory tests are assessed. If, on this basis, it is judged that there is no risk of use of the product resulting in the acceptance values being exceeded, the product is regarded as acceptable without further tests. If, on the other hand, the acceptance values are exceeded, the product cannot be authorised without lysimeter tests or field tests that – assessed on the basis of a "realistic worst case" situation with respect to used dosages, conditions of use, climate, etc. – prove that use of the product does not imply an unacceptable risk of persistence, leaching to the groundwater and bioaccumulation.
1.2 Risk of effects on aquatic and terrestrial organisms
For the impact area, the risk assessment is based on the so-called quotient method, in which the relationship between toxicity and exposure is calculated, cf. The Uniform Principles, EU’s Council Directive 97/57/EEC.
1.3 Toxicity
It is judged whether the exposure exceeds the toxic level with a ³ 1 x (un)certainty factor of between 5 and 1,000, depending on the organism and on whether the toxicity is acute or chronic.
The higher the quotient, i.e. the lower the exposure and/or toxicity, the lower the risk from use of the substance.
The exposure (PEC = Predicted Environmental Concentration) is estimated on the basis of the intended use with respect to dosage, method of application, time of use, plant cover, etc.
The (un)certainty factor is intended to cover the variation in sensitivity between species, extrapolation from acute to chronic effects and from laboratory to field, etc.
The risk assessment is performed in stages. The first stage is a rough estimate of PEC. If this concentration lies much (corresponding to at least the (un)certainty factor) below the effect concentrations achieved in the laboratory, the pesticide is regarded as acceptable with respect to the area investigated without further analyses. If, on the other hand, the effect concentration is close to PEC, one moves to the next step, in which the PEC calculation is refined so that PEC again approaches a "realistic worst case". In cases in which a "realistic worst case" PEC and the concentration that produces toxic effects are close to each other (are less than the (un)certainty factor), the product cannot be authorised without relevant semi-field and field tests of effects on aquatic and terrestrial organisms that prove that use does not imply unacceptable effects on aquatic or terrestrial organisms.
As an example, in the analysis of the risk to aquatic organisms, it is initially assumed that watercourses are directly sprayed. If the acceptable limit values are exceeded, PEC is modified on the basis of an assumption that a certain distance to watercourses is maintained. In addition, the degradation of the substance is included in the case of chronic effects and several successive applications. If the acceptable limit values are still exceeded, different forms of field studies, typically mesocosm tests are included in the analysis. In such cases, the safety factor may have to be reduced because far more species will usually be represented in field studies and because field studies mean more realistic exposure conditions than laboratory tests. The field studies may mean that substances judged on the basis of laboratory tests to be unacceptable in relation to the prescribed acceptance level are deemed acceptable on the basis of field studies.
The conclusion of the Danish review in 1997 is that all pesticides authorised since June 1993 fulfil the minimum requirements set out in "Framework for Assessment of Plant Protection Products". Products reviewed before June 1993 are assessed in relation to the "criteria" applying at that time, which are largely based on the substances’ inherent properties.
2 Classification of health impacts
2.1 Classification of carcinogenicity, mutagenicity and reproduction toxicity
Classification of substances for the above-mentioned effects are generally based on the following considerations:
 | What properties does the substance have (qualitative)? |
| How well documented are these properties? |
| Are the properties of relevance to humans? |
There are three categories for carcinogenicity, impairment of fertility and mutagenicity. The categories differentiate between the reliability of the evidence. The classification is therefore based mainly on qualitative assessments and evidence. For these three effect groups, the potency of the substance is not specifically included in the assessment to decide the category in which it is to be classified. In other words, the highest dose that does not cause adverse effect levels (NOAEL) is not included in the assessment. However, in the case of substances that are toxic for reproduction , if the effects are only seen in very high dosages, this must be taken into consideration when assessing whether the substance should be classified at all for the effects. Reproduction toxicity covers both damage to the foetus and impairment of fertility.
Category 1
Carcinogenic (Carc, Cat1), mutagenic (Muta, Cat 1) or reproduction toxicity (Rep, Cat1).
| For all three, there must be epidemiological studies showing the effect of the substances. That is very rare in practice, particularly for mutagenicity, because it is often very difficult to draw any clear conclusions from the results of such studies. |
Category 2
Carc, Cat2.
| Substances that are clearly carcinogenic in two animal species or substances that are clearly carcinogenic in one animal species, supported by mutagenicity or structural similarities to other substances that are classified as carcinogenic in category 1 or 2. |
Muta, Cat2.
| Substances that are clearly mutagenic in gametes in vivo. |
Rep, Cat2.
| Damage to progeny: Substances clearly shown to damage the progeny in one or more animal species and where the effect is not secondary to the effect on the dam. |
| Impairment of fertility: Substances shown to reduce fertility in animal tests, supported by documentation for the mechanism of action or structural similarity to other substances that are classified as being toxic for reproduction in category 1 or 2. |
Category 3
Carc, Cat3.
| Substances suspected of being carcinogenic, but where the evidence is not sufficient to classify the substance in either category 1 or category 2. This may be because the substance has not been sufficiently investigated, but the data that are available indicate that the substance is carcinogenic. A substance may also be classified in category 3 when it has been sufficiently investigated, but where the data are ambiguous. In these cases there will normally be no sign of mutagenicity. Substances that are carcinogenic through a hormonal mechanism will not normally be classified higher than category 3. This is because hormonal effects are generally assumed to be dose-related. In other words, there exists a threshold dose, which means that if one is exposed to less than this dose, there is no risk of developing cancer. |
Muta, Cat3.
| Substances that are mutagenic in in vivo systems on somatic cells (i.e. all cells that are not gametes), but where there is no evidence of effects in gametes. If the substance is only positive in in vitro tests, it will normally not be classified unless no in vivo tests at all have been performed and the in vitro results are very convincing and the substance also has points of similarity with other substances with known damaging effect on the genetic material. |
Rep, Cat3
| Damage to progeny: Substances that are teratogenic but where the effect is not clear or where the damage is doubtful. There can be problems in judging whether the damage is a secondary effect of toxicity to the dams. |
| Impairment of fertility: Substances that reduce fertility without this being a secondary effect of general toxicity, but where the results are unclear. For example, the Danish Environmental Protection Agency has classified substances in this group if there have been tests that show that the substance inhibits testosterone synthesis or destroys the sperm-producing tissue, even though no direct effect has been seen on fertility in a multi-generational test (which is the test in which one normally sees effects on fertility). |
2.2 Other long-term damage (chronic toxicity)
For chronic toxicity, a substance can be classified with the phrase R48 (Danger of serious damage to health by prolonged exposure) if serious long-term effects have been seen. To this, another phrase is added, describing partly the administration path (swallowing, skin contact or inhalation) where the substance caused the observed effects and partly the dose level. In other words, there is primarily a qualitative assessment, which leads to a conclusion about whether the long-term effects observed are serious enough for classification. The lowest effective dose (LOAEL = Lowest Observed Adverse Effect Level) is then taken into account in the final assessment of whether the substance must be classified, since it is a requirement for classification that the effects occur at a dose below a specific level. LOAEL is also included in the assessment of the phrase to be affixed to R48. For example, one can have a classification that is called R48/22: "Harmful: danger of serious damage to health by prolonged exposure if swallowed" or R48/25: "Toxic: danger of serious damage to health by prolonged exposure if swallowed", with the latter indicating a more potent substance than the former, both classifications being based on tests in which the substance is administered by mouth.
When classifying for chronic toxicity, the authorities naturally also assess the evidence, but there are not differentiated groups for more or less well-documented effects.
R48 is a classification that is used in connection with a wide range of long-term effects – for example, anaemia, cataract, reduced immune defence and damage to the central nervous system (CNS). In the case of CNS, specific studies are not required today because there are no established guidelines in this area. One may see certain signs of CNS damage from long-term studies, but cannot determine a specific effect with any certainty. Effects that are not regarded as "serious" and that are therefore not classified with R48 include changes in organ weights without signs of functional disturbances, species-specific effects and small changes in biochemical parameters that are of doubtful toxicological significance.
A substance can also be classified with R39 (Danger of very serious irreversible effects) if irreversible damage has been observed from a single exposure.
The classification rules used in Denmark are used throughout the EU. The rules are regularly revised and expanded and are regarded as a reasonable and usable system for describing the inherent toxicological properties of chemical substances.
3 Short-term risk to health
Products with moderate and high acute toxicity are classified as Toxic or Very toxic. These classifications include toxicity if swallowed, if in contact with skin or if inhaled. The effects are measured by means of the LD50 method (the dose that kills 50% of the animals when administered by the path in question). The Executive Order on Pesticides includes minimum limits for LD50 for classification as Harmful, Toxic or Very Toxic for both solids and liquids. Caustic products are classified with R34 (Causes burns). If the substance is not caustic but still causes serious eye damage, it is classified with R41 (Risk of serious damage to eyes).