Human Health Risk Assessment - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 238

10% response. The T25 corresponds to the chronic exposure rate, which will result
in tumours with 25% of the animals at a specific tissue site, after correction for
spontaneous tumour incidence (Dybing et al. 1997 ).
Another approach which is gaining attention in Human Health Risk Assessment
for non-threshold carcinogens is the Margin of Exposure (MOE) approach. In that
approach, a reference point from the dose-response curve is taken and the actual
human exposure is compared with that reference point. The ratio between the expo-
sure at the reference point and actual human exposure is called the MOE and
determines the decision on health risk (EFSA 2005 ). In regard to Risk Assessment
at the EU level, the T25 or the BMDL 10 are recommended as a reference point
(EFSA 2005 ; ECHA 2008 ). For its application in Human Health Risk Assessment,
guidance is needed on the acceptable value for the MOE. EFSA ( 2005 ) considers
that a MOE of 10,000 or higher based on a BMDL 10 from an animal study is of low
concern. If a T25 is used, the additional uncertainty should be taken into account.
This approach is used in the contaminated sites framework of the UK. The resulting
Critical Exposure value is defined as an Index Dose (ID).
Critical Exposure values for non-threshold contaminants will be derived for that
route or those routes of exposure causing the non-threshold effect.
The derivation of Toxicological Reference Values for threshold contaminants are
described in detail in Langley ( Chapter 12 of this topic).

5.4.5 Reliability

If the Critical Exposure values are derived from well-documented human data, then
the accuracy can be high and uncertainty will mainly arise from uncertainty in the
dose-response data itself. In comparison, Critical Exposure values derived from
animal studies have an uncertainty resulting from the precision in the toxicologi-
cal studies and from the assessment factors derived. The precision of the Critical
Exposure values is inversely related to the assessment factors applied (Speijers
1999 ). Since Toxicological Reference Values for humans are generally derived indi-
rectly, that is , from experimental animal data and assessment factors, the accuracy of
these values is limited. The uncertainty of Critical Exposure values is also reflected
in their definitions. As an example, the definition of Reference Dose is given as: 'The
reference dose (RfD) provides quantitative information for use in Risk Assessments
for health effects known or assumed to be produced through a nonlinear (possi-
bly threshold) mode of action'. The RfD (expressed in units of mg d − 1 )is

defined as an estimate (with uncertainty spanning perhaps an order of magnitude)
of a daily exposure to the human population (including sensitive subgroups) that is
likely to be without an appreciable risk of deleterious effects over a lifetime.
A critical factor with regard to Toxicological Reference Values, and Human
Health Risk Assessment in general, is that less knowledge often results in a more
stringent Toxicological Reference Value. Or, as formulated in Lindley ( 2001 ), the
less epidemiologists know about us as individuals, the more at risk the public

kg bw − 1

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