Human Health Risk Assessment - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 233

The derivation of Toxicological Reference Values depends on the type of associ-
ated effects, that is, threshold or non-threshold effects . Generally, non-carcinogenic
contaminants are considered as contaminants with a threshold effect. For this
type of contaminants, a Critical Exposure value can be derived as a threshold
for which adverse effects on humans are unlikely to occur when this Critical
Exposure is not exceeded. For carcinogenic contaminants the threshold approach
is not always applicable. For the category of non-genotoxic carcinogenic con-
taminants, a threshold Critical Exposure may apply. On the contrary, genotoxic
carcinogenic contaminants, that is, contaminants that directly cause mutations
in DNA-material which could result in cancer, are generally considered as non-
threshold contaminants. A safe threshold is assumed not to exist for most genotoxic
carcinogenic contaminants. In fact, exposure to the smallest possible amount of
these contaminants (i.e., one single molecule) increases the risk for cancer.
It must be noted, however, that not all non-carcinogenic effects can be related to
a threshold.
The same contaminants can show both threshold and non-threshold effects and
the type of effect can differ by route of exposure (oral, inhalation, or dermal).
However, if a contaminant shows non-threshold carcinogenic effects, these effects
will generally be the most critical effects. In that case, the contaminant is treated as
a non-threshold carcinogen.
Traditionally, there has been a lot of discussion about Toxicological Reference
Values. The critical effect of low-level lead exposure in children, as one example,
is on the central nervous system and relates to cognitive impairment. For years,
a threshold of 10 g lead/dL blood has been considered as safe. Recent research

has demonstrated that this threshold should be reviewed and that the absence of
a threshold could not be excluded (Chiodo et al. 2007 ; Rossi 2008 ). Arsenic, as
another example, is a genotoxic carcinogen by the oral route, but discussion upon
the presence or absence of a threshold is still ongoing (ATSDR 2007 ).
Additional details on threshold and non-threshold effects are described in
Langley ( Chapter 12 of this topic).

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5.4.3 Toxicological Reference Value for Threshold Contaminants

5.4.3.1 Principles

For threshold effects, a rather universal approach is followed. A level, below which
it is believed that no adverse effects will occur, is derived from the No-observed-
adverse-effect-level (NOAEL) and assessment factors. Alternatively, exposure is
compared directly to the NOAEL and a margin-of-exposure or margin-of-safety is
calculated, although this method is less useful for the derivation of Soil Quality
Standards. Another approach, using the whole dose-response curve, is the bench-
mark approach. In this approach, the threshold level is derived by applying a
statistical regression on the dose-response curve (International Programme on
Chemical Safety 1999 ).