Risk assessment tiered approach

This chapter has outlined the general principles of the use of extrapolation in criteria setting and risk assessment. Extrapolation is used in the setting of criteria, where only effects are considered, as well as in risk assessments, where both effects and exposures are considered. In formulating approaches to criteria setting and risk assessment, tiers are often used to simplify the process. In keeping with the... 

In human risk assessment, tier 4 approaches would require PBPK modeling, BRN models, or other highly specific approaches. In ecological risk assessment, emphasis can be put on modes of action in relation to subgroups of exposed species (e.g., insecticidal action and focus on impacts on insects). This type of approach was proposed some years ago (Posthuma et al. 2002), and has been applied in the evaluation of pesticide risks (De Zwart 2005 Henning-de Jong et al. 2008). 

Interest has been expressed in the possibility of using biomarker assays as a part of risk assessment for regulatory purposes, and some workers have suggested tiered testing procedures that follow this approach (see, for example, Handy et al. 2003). It is to be hoped that regulatory schemes, such as that of REACH (see European Union 2003), will be sufficiently flexible to incorporate new assays and testing strategies as the science advances. 

It is advisable, then, in a tiered approach to concentrate first on crops and activities (scenarios) that are considered to be relevant with respect to the expected level of exposure and to exclude those not relevant. Second, whether or not the toxicological properties of the product may lead to general restrictions on re-entry should be investigated. If both the likelihood of reentry and the hazard due to the toxicity of the compound cannot generally be neglected, a risk assessment over several steps should be carried out. The assessment may be based on surrogate data and "worst-case" assumptions at first and then refined, if necessary. One possible approach to a tiered evaluation procedure is presented in Figure 1. 

Because the whole idea of a tiered approach of the kind outlined above is in its initial stages, it will have to be validated and discussed further and will in all probability need to be refined afterwards. The aim here is to introduce the idea of a stepwise approach to the assessment of the risk to re-entry workers. The outlined procedure should be used to calculate the dermal re-entry exposure for real examples of rather dermally toxic compounds in order to gain experience with the recommended procedure. 

Fig. 2 Scheme of the tiered approach of the European Medicines Evaluation Agency (EMEA) for environmental risk assessment... 

Data used to describe variation are ideally representative of some population of risk assessment interest. Representativeness was a focus of an earlier workshop on selection of distributions (USEPA 1998). The role of problem formulation is emphasized. In case of representativeness issues, some adjustment of the data may be possible, perhaps based on a mechanistic or statistical model. Statistical random-effects models may be useful in situations where the model includes distributions among as well as within populations. However, simple approaches may be adequate, depending on the assessment tier, such as an attempt to characterize quantitatively the consequences of assuming the data to be representative. 

Giddings JM, Anderson TA, Hall LW, Kendall RJ, Richards RP, Solomon KR, Williams WM. 2000. Aquatic ecological risk assessment of atrazine a tiered, probabilistic approach. Novartis 709-00. Greensboro (NC) Novartis Crop Protection. 

A tiered approach is also used for calculating estimated residues in animal commodities (meat, milk, and eggs), and higher-tier calculations can have a significant impact in decreasing estimates of dietary exposure and risk. The Tier III assessment for atrazine and simazine (Tables 27.3 and 27.4) is based on calculations of the estimated theoretical residue in animal commodities, whereas the Tier I assessments use tolerance values. These theoretical residues are often referred to as secondary residues. Calculations for estimating secondary residues in animal commodities are performed by constructing livestock (beef, dairy, and poultry) diets comprised of treated feed items to obtain a... 

Parkhurst, B.R., W. Warren-Hicks, R.D. Cardwell, J. Volison, T. Etchison, J.B. Butcher, and S.M. Covington (1996). Aquatic ecological risk assessment A multi-tiered approach to risk assessment, 91-AER-l. Alexandria, VA Water Environment Research Foundation. 

Tiering is often applied in risk assessment in order to reduce expenditures in time, money, and labor when the assessment requires only simple and possibly conservative output. Table 5.3 provides a suggested tiered approach in mixture extrapolation and is further described in the bulleted list below. The tiering is based on the way that mixture mechanisms are addressed in the approach. It is assumed that issues such as matrix and media extrapolation have been addressed according to the methods described in the pertinent chapters. 

There are many extrapolation methods, of different complexities, and with different purposes and suitabilities for prospective and retrospective risk assessments. A compilation of the methods is insufficient to guide the choice of procedures to use when assessors need to conduct risk assessments. Therefore, a practical and pragmatic guide to extrapolations and their everyday use is provided in the last chapter. It defines a general stepwise approach to identifying the types of extrapolation (matrix and media, (Q)SARs, mixtures, etc.) that are most relevant for an assessment problem, and it defines an overall approach to the assignment of tiers. 

Various tiered risk assessment schemes have been published for some examples, see Table 10.1. Tiered approaches are used to address risk problems for classical chemical substances, pharmaceuticals, pathogens, and so forth, for both ecological and human risk assessments. 

Some examples of risk assessment systems with a tiered approach... 

In the different risk assessment approaches that exist (e.g., Table 10.1), there are different ways to combine the 3 axes, in prescribing the approaches that are needed to address the specific problem, collect the data, and handle the data and models. Due to their different origins and the different problems that they address, the existing tiered systems are thus very different. One method is, however, not necessarily better or worse than the other. For this guidance, we have organized the methods according to the method characteristics themselves, not to existing tiered frameworks. 

A proposal for conceptual tiering of extrapolation approaches in ecological risk assessment... 

Assessors should base their selection of methods on clearly defined decision criteria, and they need to communicate the results using clear and transparent language. This includes statements on the extrapolation issues that were considered but not addressed, and the magnitude and direction of the bias that may have been introduced by the extrapolation or lack thereof. In lower tiers and prospective risk assessment, this should lead to setting more appropriate UFs and ensure that lower tier approaches are more conservative than higher tier approaches. All this helps assessors to make informed decisions, on one hand, but it also allows the identification of future research needs, on the other hand, especially when methods are not available. 

The level of detail of the uncertainty analysis should be based on a tiered approach and consistent with the overall scope and purpose of the exposure and risk assessment. 

Typically, exposure and risk assessments conducted during regulatory evaluations are performed in a tiered or phased approach. A tiered approach refers to a process in which the exposure or risk assessment progresses systematically from relatively simple to more complex. An important feature of a tiered analysis is that the exposure or risk assessment and the accompanying uncertainty analysis may be refined in successive iterations. 

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