Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 548

event was considered sufficient to initiate the process that leads to the development
of cancer. In contrast, the dose-response was assumed to have a threshold for non-
cancer effects, the assumption being that, for non-cancer effects, there is a dose
below which the risk of adverse effects will be nil; in effect, that there is a “safe”
dose.
In more recent times, as it has become evident that not all carcinogens have geno-
toxicity as their prime mode of action (Ashby and Tennant 1991 ), the dose-response
curve has often been assumed to be non-threshold for genotoxic carcinogens
and threshold for non-genotoxic carcinogens in countries such as Canada and
some European countries (Whysner and Williams 1992 ; Health Council of The
Netherlands 1994 ) and in the WHO Drinking Water Guidelines (WHO 1993 ).
However, the WHO considered that these approaches are not suitable to the devel-
opment of generic guidance values in Environmental Health Criteria documents
because they “ ... require socio-political judgements of acceptable health risks”

(WHO 1994 ).
In these examples, the distinction between a genotoxic carcinogen and a non-
genotoxic carcinogen is a science policy decision for regulatory purposes and does
not necessarily reflect the mechanism of carcinogenesis. It does not mean that a
non-genotoxic carcinogen does not affect the genetic material of the cell under
some circumstances, nor that a genotoxic effect is the only event required for the
development of cancer by a genotoxic carcinogen.
With advances in biological knowledge, mechanistic data, pharmacokinetic data
and other relevant data are increasingly being taken into account in classifying and
assessing the risks of carcinogens. The US EPA has revised its guidelines for car-
cinogen Risk Assessment (US EPA 2005 ) and they stress the importance of “a
critical analysis of all of the available information that is relevant to assessing the
carcinogenic risk as the starting point from which a default option may be invoked if
needed to address uncertainty or the absence of critical information” (p. 1.11).The
use of mode of action in the assessment of potential carcinogens is a main focus
of these cancer guidelines as a result of “the significant scientific advances that
have developed concerning the causes of cancer induction” (p. 1.10). The guide-
lines also emphasise uncertainty analysis in the Risk Assessment process and “the
importance of weighing all of the evidence in reaching conclusions about the human
carcinogenic potential of contaminant” (p. 1.7).

12.5.3 Threshold Approaches

A threshold is considered to occur because of biological mechanisms such as the
ability to metabolise or excrete a toxin or to repair damage up to a certain dose.
The approach with these models is to derive exposure limits such as an ADI, a
Provisional Tolerable Weekly Intake (PTWI), Tolerable Daily Intake (TDI) or RfD
(Barnes and Dourson 1988 ; Dourson et al. 1996 ;WHO 1994 ). This approach makes
no attempt to calculate a level of risk at low exposures. Rather, it derives a dose
which is apparently without effect in a human population or suitable animal model,