Risk assessment dose-response characterisation

In recent years it has become increasingly apparent that for chemical contaminants that are abundant in the environment a more sophisticated approach to dose-response characterisation is required. There is increasing evidence that small but significant sub-populations are exposed to intakes that exceed PTWIs and most people are exposed to potential carcinogens through their diet. In such cases the PTWI concept is redundant because it is necessary to assess the actual levels of risk to which individuals are exposed in order to introduce proportionate control measures. Simply knowing that the hazard exists is not sufficient. 

In section 2.3 of this chapter the present approach to characterisation of dose-response relationships was described. In most cases it is necessary to extrapolate from animal species that are used in testing to humans. It may also be necessary to extrapolate from experimental conditions to real human exposures. At the present time default assumptions (which are assumed to be conservative) are applied to convert experimental data into predictive human risk assessments. However, the rates at which a particular substance is adsorbed, distributed, metabolised and excreted can vary considerably between animal species and this can introduce considerable uncertainties into the risk assessment process. The aim of PB-PK models is to quantify these differences as far as possible and so to be able to make more reliable extrapolations. 

In the concept proposed in 1983 in the US, risk assessment comprised of four steps, namely, hazard identification, dose-response analysis, exposure analysis, and risk characterisation. In a simplified procedure of risk assessment, only three types of information is needed, namely, physico-chemical characteristics, toxicology, the behavior of the chemical at the use situation. The physicochemical data is supposed to show some sense of toxicity and behaviour of the chemical. The toxicology data shows the kind of symptoms to be elucidated, the target organism, and the amount of chemicals needed for showing the symptoms. Behaviour data would show the extent the receptor - here, humans or other natural organisms - is contacted by the chemical at the use situation. The risk assessment is simply to compare the extent the receptor is contacted and the amount of the chemicals needed to show the symptom. 

Ideally, a health risk assessment would characterise the dose-response relationship, i.e. the relationship between the dose of a chemical administered or received and the incidence and/or severity of an adverse health effect in an exposed population. However, estimating the dose-response relationship for many chemicals (particularly environmental agents) is often extremely difficult or, because of the lack of data, unachievable. For example, little is known about dermal uptake rates of soil-bound contaminants or the duration of such contact episodes. Therefore, estimating the dose received from dermal contact with soil can be highly tentative and is usually based upon a number of simplifying assumptions. 

Risk characterisation integrates data from hazard identification, dose-response and exposure assessments to describe the overall risk from a pesticide. It develops a qualitative or quantitative estimate of the likelihood that any of the hazards associated with the pesticide will occur in exposed people. It also involves the assumptions used in assessing exposure as well as the uncertainties that are built into the dose-response assessment [3]. 

Risk assessment is a multidisciplinary task related to toxicology, analytical chemistry, biochemistry, molecular biology, health disciplines, politics, etc. The four key aspects of risk assessment are hazard identification, dose response, exposure assessment and risk characterisation. They are all driven by dynamics based on intake, absorption and effect. 

The risk assessment entails the hazard identification and, as appropriate, dose (concentration) response (effect) assessment, exposure assessment and risk characterisation. 

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