Field research for the authorisation of pesticides

The Minister of Public Health, Welfare and Sport, also on behalf of other members of the goverment, has requested the Health Council to review the role that results from field research can play in ecotoxicological risk assessment for the authorisation of pesticides. In this advisory report a committee of the Health Council complies with this request. It interprets the term ’field research’ in its broadest sense: the Committee understands field research to mean all of the research that exceeds the level of the standard ’single-species’ toxicity test in the laboratory. This might include ’multi-species’ toxicity tests in the laboratory, research on model ecosystems in the laboratory, glasshouse or in the open air and tests in ditches, field margins, agricultural fields etc. Within this category the Committee also includes tests aimed at studying the behaviour of a pesticide in intact soil profiles. What is common to investigations of this kind is the fact that they set out to achieve a closer approximation of the field situation. The Committee confines itself to the agricultural pesticides (plant protection products). These are used to protect agricultural crops or to keep uncultivated land free of weeds.

Legislation and authorisation procedure

The authorisation (registration) of pesticides in the Netherlands is regulated in the Pesticides Act. This stipulates that compounds may only be brought onto the market if, when used as directed, they are sufficiently effective and do not cause any unacceptable damage to the crop, to humans, to plants and animals (except target organisms), or to water and soil quality. A more detailed elaboration of the environmental requirements for plant protection products can be found in the Pesticides Environmental Authorisation Requirements Decree. Dutch legislation has to a great extent been brought into line with the European Union directives in this area - the Authorisations Directive and the so-called ’Uniform Principles’.

The Board for the Authorisation of Pesticides (CTB) evaluates the acceptability of pesticides in the Netherlands on behalf of the government. This evaluation is performed with reference to a dossier which the applicant (usually the manufacturer or importer) must submit with its application for authorisation. This dossier contains data about the use of the substance, its physical and chemical properties and its toxicity for certain standard test organisms. In answering the question of whether a given compound satisfies the environmental requirements, the CTB follows a ’tiered approach’. The first tier comprises a broad, relatively stringent evaluation — based on model calculations — of the behaviour of the substance in the environment and of the submitted toxicity data. A substance which, according to that evaluation, satisfies the environmental requirements is considered to be acceptable - at least as far as environmental safety is concerned. Otherwise, the applicant is given the opportunity to submit additional research data. Based on this data, a renewed evaluation of environmental risks takes place (the second tier). If it appears likely from this data that the requirements are not exceeded under field conditions or that no unacceptable effects will occur, the substance is still authorised. In case of doubt, it is possible to issue a restricted authorisation, which is contingent upon research conducted under field conditions. Based on the resultant data, a definitive assessment is then carried out (the third tier). Every plant protection product that receives authorisation must be regularly reviewed. This usually takes place every five years.

Field research prior to authorisation

Field research is one of the ways in which an applicant can obtain the additional data for the second tier of the risk assessment. Because this is carried out prior to authorisation, the Committee speaks of pre-registration research. In an international context, guidelines have been established for the design and execution of various sorts of field research.

The Committee believes that this type of research can provide valuable additional data about the behaviour of plant protection products in the field, the exposure of non-target organisms and the resultant effects at population, community and ecosystem level. Experience gathered to date has shown, however, that it is frequently unclear how that data might be (or would need to be) used in reaching a decision about authorisation. The Committee discusses the causes and makes recommendations for improvements. It is of the opinion that it is not possible to reach a decision about the authorisation of a plant protection product until it has been clearly specified what is understood by an ’unacceptable effect’. Clarification of this point has both a policy-related and a scientific aspect. The former aspect concerns the government’s protection goals. In the Committee’s opinion, these have not been sufficiently clearly formulated in the Pesticides Environmental Authorisation Requirements Decree and in the Uniform Principles. For example, it is unclear whether the government wishes to protect organisms at a species level or at a higher taxonomic level, or whether it primarily wishes to preserve functions (pollination, soil mixing, predation, etc.). The scientific aspect relates to the ecological significance of effects. The response of populations and communities of organisms in shallow, fresh water to exposure to plant protection products is relatively well known. This applies to a much lesser extent in relation to other populations and communities. It is therefore unclear what induced changes mean for the fulfilment of the protection goals. For these populations and communities, it is, for the time being, still only possible to draw the line between acceptable and unacceptable effects with an ample safety margin. This, according to the Committee, is one of the main reasons for the problems that are encountered in interpreting the results of field trials for the purposes of decisions about authorisation. The Committee believes that criteria and preconditions need to be developed in order to identify what the acceptable (or unacceptable) ecological effects are.

Recoverability could, according to the Committee, play a role in decision-making about the authorisation of plant protection products. However, we need to specify precisely what it is that is recovering and ask ourselves whether the original changes have not, in turn, led to other, lasting developments. In the latter case, we need to ask ourselves what the ecological significance of such developments is and whether they are incompatible with the protection goals.

The Committee recommends setting up field trials with a view to investigating possible effects of plant protection products on organisms according to a multi-concentration design, whereby systems that have been treated with different dosages of a compound are compared with untreated control systems. It regards a solid statistical input as an essential element in setting up such a trial and analysing the measurement results that are obtained. The Committee points out that designing field trials for the purpose of demonstrating the absence of previously (i.e. in the first tier) presumed effects, places great demands on the quality of the trial, especially with regard to its statistical power. This must be sufficient to allow for the detection of changes that might be regarded as ecologically relevant. Only then does the absence of a statistically significant effect mean that there has, in all probability, been no ecologically relevant effect. When presenting NOEC values, the Committee recommends recording the limits of the (95%) confidence interval for the true effect.

A field trial can only be used in assessing the acceptability of a plant protection product if it is possible to deduce from the results whether, under the broad range of field conditions, no effects will emerge that might be regarded as unacceptable. This can best be guaranteed by conducting several tests under different conditions, but this appears not to be feasible in most cases for reasons of cost. In that case, the Committee considers a realistic worst case approach to be a good alternative.

Field research following authorisation

If, after the second tier in the risk assessment, there is still any uncertainty about the safety of the plant protection product, it may be sensible to grant a substance a restricted authorisation on the condition that further field research is conducted into the environmental effects under field conditions. The results can be used for a third tier in the risk assessment procedure. Because investigators will then usually have a clearly defined research question, which has been dictated by all previous research results, and because this research takes place after (restricted) authorisation, the Committee speaks of targeted post-registration field research. This tends to be of a descriptive nature (monitoring) and must be regarded as being supplementary to earlier experimental research. The results will frequently exhibit a greater dispersion than pre-registration research, but they may, on the other hand, be able to give a better picture of the spatial and temporal variability in the behaviour of the substance and the occurrence of effects, especially if geostatistical techniques are employed. It is unclear, however, what role this information should play in decision-making for authorisation purposes. This is because there is still no spatial or temporal dimension in the government’s protection goals.

In order to validate the authorisation procedure, the Committee recommends that a finger should also be kept on the pulse in relation to authorised compounds by conducting research into the presence of plant protection products in environmental compartments (monitoring). This monitoring does not form part of the actual authorisation procedure and is not based on concrete suspicions. The Committee therefore speaks of general post-registration field research. The selection of the substances that are to be monitored can be based on the scale of use, toxicity, mobility or degradability. The substances that are selected will preferably include representatives from all of the important groups of substances. Indications of possible effects on organisms can be obtained by comparing concentrations that have been observed in the environment with (eco)toxicologically supported standards. In addition, it is possible to compare trends in the data collected by public and private bodies about populations of plants and animals with those relating to the use and the occurrence of plant protection products. This provides an indication of the potential role that these substances might play in a possible decline in population densities. This is, in fact, the only way to detect long-term changes. Additional experimental research is then needed in order to determine whether any causal connections exist.

Unsuspected harmful effects of plant protection products can also come to light as a result of sudden mortality (possibly on a massive scale) among conspicuous animal species, such as birds, fish or honeybees. The Committee advocates that a central research bureau should be established to investigate and record these ’incidents’ and that this bureau should publish an annual report. It is not only important to investigate whether plant protection products are involved, but also whether these substances have been used as directed.

The results of general post-registration field research and incident investigations can be used in connection with the regular re-evaluation of substances or, in the case of serious suspicions, they can prompt immediate intervention in the authorisation process. This field research therefore forms a safety net for substances that have been wrongly authorised. Nevertheless, the Committee does not see any reason to subject the data that the applicant is required to provide to less rigorous requirements.

The Committee recommends that the results of field research that is carried out for the purposes of either the second tier (the pre-registration phase) or the third tier (the post-registration phase) of the risk assessment procedure should always be evaluated in connection with all previously available data. Although one can impose general rules with regard to the design and execution of field research, expert judgement will always play a role.

It is not only during the evaluation of individual substances that the results of field research are useful. They can also be used to improve the risk assessment procedure, especially the first tier. The Committee attaches great importance to research that is initiated specifically for this purpose. It can be used to validate, calibrate and (if necessary) improve fate models for the estimation of (exposure) concentrations in environmental compartments. It is also possible to evaluate both toxicity tests performed with standard test organisms in the laboratory and the applied safety factors for their suitability in estimating the risks in the field. A reliable first tier can frequently obviate the need for time-consuming and costly follow-up research for individual substances.