Deterministic exposure assessments

Selection of the appropriate metric for use in the risk assessment can have a significant impact on the outcome of an assessment. Regardless of the mathematical approach used, it is important that harmonized guidance exists for metric selection. Guidance should be based on a number of considerations, including data quality, data quantity, distribution type, duration of exposure and nature of the toxicology endpoint. Based on personal experience with numerous deterministic exposure assessments, it is clear that regulatory authorities differ with respect to input and output metric selections. 

There is a transition away from nsing a deterministic approach in which high end or upper bound point estimates and defanlt valnes are nsed towards nsing a probabilistic approach in distribntional models which incorporate complex data sets to build realistic estimates of exposure. While probabilistic dietary exposure assessments can now be carried out routinely for many pesticides, available occupational and residential exposure data sets are typically insufficiently robust. Work on developing newer exposure databases (e.g. ARTF, ORETF, AHETF and EUROPOEM II) and distributional use pattern data would facilitate this transition. The topic of probabilistic exposure assessment is covered in Chapter 8. 

TIERED APPROACHES TO EXPOSURE ASSESSMENT 144 Deterministic (Point-Estimate) Exposure Assessments 145 Probabilistic Exposure Assessments 145 REPORT WRITING 145 Protocol/User s Guide 146 General Description of Exposure Model 146 Detailed Description of Model Inputs and Outputs 146 Exposure Model Validation 146 Quality Assurance Practices 147 Archiving 147... 

The model or set of models to be used in the exposure assessment to relate the presence of a substance to human exposure/absorbed dose should be stated. The model s general description should provide enough detail so that the user or reviewer understands the input variables, underlying mathematical algorithms and data transformations and output/results, such that the model can be easily compared to other alternatives. The basis for each model, whether deterministic, empirical or statistical, should be described. The statement of the model should include which variables are measured and which are assumed. A description should be provided of how uncertainties in the parameters and the model itself are to be evaluated and treated. 

Figure 6.6 Routes for implementing exposure assessment, where (a) implements a deterministic worst-case , while (b) implements a probabilistic route...

The determination of the estimated levels of exposure is obviously a critical component of the risk assessment process. Both pesticide residue levels and food consumption estimates must be considered. Methods for determining exposure are frequently classified as deterministic and probabilistic methods (Winter, 2003). 

The environmental concentration of a stressor, either measured or estimated, is compared with an effect concentration such as an LC50 (lethal concentration to kill 50% of individuals in a theoretical population in a set period of time) or no observed effect concentration (NOEC) [31, 32]. These are simple ratios of single exposure and effects values and may be used to express hazard or relative safety. This deterministic method uses point estimates to represent one or more factors in a risk assessment and treats them as if they were fixed and precisely known [33]. The calculation of HQs... 

The ability to use probabilistic approaches to assess dietary pesticide exposure has also changed much of the emphasis of pesticide risk assessment practices from assessing long-term (chronic) exposure to short-term (acute) exposure. Deterministic approaches worked well with chronic assessments since the day-to-day variability in food consumption patterns and the variability of pesticide residue levels tended to average out over the course of a 70-year exposure period. Deterministic approaches have also often been used in the assessment of acute dietary risk by assuming an upper percentile level of food consumption and the maximum detected or allowable level of residue. The point estimate determined in this manner is then compared with the RfD to determine the acceptability of exposure under the specified conditions. 

Two types of responses from exposure to hazardous substances, called stochastic or deterministic,5 are of concern in risk assessment. The two types of responses are distinguished by the characteristic features of the dose-response relationship, i.e., the relationship between the dose of a hazardous substance and the probability (or frequency) of a response. 

Although dose-response assessments for deterministic and stochastic effects are discussed separately in this Report, it should be appreciated that many of the concepts discussed in Section 3.2.1.2 for substances that cause deterministic effects apply to substances that cause stochastic effects as well. The processes of hazard identification, including identification of the critical response, and development of data on dose-response based on studies in humans or animals are common to both types of substances. Based on the dose-response data, a NOAEL or a LOAEL can be established based on the limited ability of any study to detect statistically significant increases in responses in exposed populations compared with controls, even though the dose-response relationship is assumed not to have a threshold. Because of the assumed form of the dose-response relationship, however, NOAEL or LOAEL is not normally used as a point of departure to establish safe levels of exposure to substances causing stochastic effects. This is in contrast to the common practice for substances causing deterministic effects of establishing safe levels of exposure, such as RfDs, based on NOAEL or LOAEL (or the benchmark dose) and the use of safety and uncertainty factors. 

In many respects, the foundations and framework of the proposed risk-based hazardous waste classification system and the recommended approaches to implementation are intended to be neutral in regard to the degree of conservatism in protecting public health. With respect to calculations of risk or dose in the numerator of the risk index, important examples include (1) the recommendation that best estimates (MLEs) of probability coefficients for stochastic responses should be used for all substances that cause stochastic responses in classifying waste, rather than upper bounds (UCLs) as normally used in risk assessments for chemicals that induce stochastic effects, and (2) the recommended approach to estimating threshold doses of substances that induce deterministic effects in humans based on lower confidence limits of benchmark doses obtained from studies in humans or animals. Similarly, NCRP believes that the allowable (negligible or acceptable) risks or doses in the denominator of the risk index should be consistent with values used in health protection of the public in other routine exposure situations. NCRP does not believe that the allowable risks or doses assumed for purposes of waste classification should include margins of safety that are not applied in other situations. 

Given the tiered system, evidently, any step in the exposure and effects assessment can be considered in a deterministic or probabilistic way. This does affect the outcomes of the risk assessment, but it does not influence the choice of extrapolation methods as guided by the decision tree itself. 

Traditionally, risk characterization is based on a deterministic approach, meaning that the risk is based on a point estimate, usually the worst-case value for each input variable (worst-case NOAELs, assessment factors, and exposure levels). This worst-case approach is intended to ensure that even the most sensitive part of the population is protected under all conditions, and therefore generally overestimates the health risk. In the case of food allergens, the maximum consumption of a food may be multiplied by the maximum concentration of the allergen in this food. This results in the maximum estimate of the intake of the allergen. If this intake is higher than the lowest threshold observed, a possible reaction to the allergen cannot be ruled out. 

Uncertainties assessed at Tier 2 (deterministic) generate alternative point estimates for exposure and may be communicated in various ways, depending on the particular methods used for sensitivity analysis. As a minimum, this should identify which sources of uncertainty have been treated at Tier 2, state and justify the alternative quantitative estimates used for each one (e.g. minimum, maximum and most likely values), present exposure estimates for those combinations of alternative estimates that are considered plausible and state and justify any combinations of estimates that are considered implausible. In addition, it will be useful (especially if upper estimates exceed levels of concern) to show which of the quantified uncertainties have most influence on the outcome. 

It is essential to provide decision-makers with an assessment of the overall degree of uncertainty in the assessment outcome. Therefore, if the uncertainties for an assessment have been analysed at different tiers (qualitatively, deterministically and probabilistically), it is necessary to find a way of presenting the results together and arriving at an overall characterization of exposure. This is difficult and subjective but unavoidable, since it is never possible to quantify all uncertainties objectively. Few assessments have attempted to do this in a systematic way, and it would be premature to give firm recommendations. However, a combined presentation should include ... 

Different safety factors may have been used in the derivation of the reference values of the individual substances (RfDA deterministic HI thus sums risk ratios that may reflect different percentile values of a risk probability distribution. Assessment and interpretation of the uncertainty in the HI may be severely hampered by this summation of dissimilar distribution parameters. In a probabilistic risk assessment, the uncertainty in the exposure and reference values is often characterized by lognormal distributions. The ratio of 2 lognormal distributions also is a lognormal distribution. The variance in a quotient of 2 random variables can be approximated as follows (Mood et al. 1974, p 181) ... 

Residential exposure should be estimated by taking into account distributions of exposure factors. Methods to assess distributions are through the deterministic or probabilistic approach (Figure 6.6). The former is often taken in preventive risk assessment in which each default value is determined from each distribution as a reasonable worst-case . The estimated exposures for the deterministic approach are expected to occur in the upper range. For actual risk assessments, the probabilistic approach directly uses the parameter distributions instead of single values to calculate distributions of exposure. To characterize exposure, an... 

First, individuals interpreting data must decide on whether to use a deterministic or a probabilistic approach to generate an exposure estimate for the analysis. The deterministic approach (point-estimate) is widespread and beginning with this approach is consistent with the tiered approach to exposure and risk assessment. 

Guidance for selecting an appropriate mathematical approach for a given exposure scenario (deterministic versus probabilistic) and guidance regarding conduct of acceptable probabilistic assessments. 

Deterministic models are used to estimate chronic, or long-term, dietary exposures. Although research is currently being conducted on the use of distributional techniques for chronic dietary risk assessment, the author is not aware of any working model at this time. 

It is frequently stated that probabilistic methods require more data than deterministic methods. This is not literally true it is possible to perform probabilistic calculations with input distributions based on small datasets or expert judgement. It is true that distributions derived from small datasets or expert judgement are likely to be very uncertain. However, if these uncertainties can be adequately represented within the probabilistic assessment, or dealt with by making conservative assumptions for the affected inputs, then probabilistic methods should still provide a useful refinement. Even in those cases where the uncertainties are too great to provide reliable estimates of exposure, probabilistic analysis may still be useful as a form of sensitivity analysis to identify priorities for data collection. 

Ecological risk may be expressed in a variety of ways. While some ecological risk assessments may provide true probabilistic estimates of both the adverse effect and exposure elements, others may be deterministic or even... 

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