Environmental Engineering Reference
In-Depth Information
5.4.4 Toxicological Reference Values for Non-Threshold
Contaminants
For genotoxic carcinogens, it is assumed that any interaction of a contaminant with
the genetic material in the human body results in a probability of an adverse effect
(McMichael and Woodward
1999
). Thus, even the lowest exposure would result
in a risk for the occurrence of cancer. Although, it is often assumed that a linear
relationship between exposure and cancer risk exists over a wide range of exposures,
there are indications of deviations from linearity. These are based on the knowledge
that cancer occurs through a multi-step process and that DNA repair mechanisms
are able to cope with low levels of DNA damage (EFSA
2005
).
The approach for the derivation of non-threshold effects is less uniform than for
threshold effects (International Programme on Chemical Safety
1999
). However,
Critical Exposure values for non-threshold carcinogens are mostly derived from ani-
mal experiments in which high doses are applied to identify a statistically significant
tumour incidence. The dose-response at these high doses needs to be extrapolated
to a risk at the lower doses occurring during environmental exposures of humans.
This extrapolation often spans several orders of magnitude.
In several guidance documents, Critical Exposure values for non-threshold car-
cinogens are derived from low-exposure extrapolation, using various extrapolation
models. At low exposures, a linear increase of risk with dose is assumed. Therefore,
the cancer risk is derived from the
Unit risk
value (i.e., the excess cancer risk per
unit of exposure or concentration ([
d
−
1
]
−
1
or [mg/L]
−
1
), aka:
Slope
factor
. Unit risk values are generally derived for lifetime exposure. For example,
a unit risk of 2.10
−
3
kg
bw
−
1
μ
g
·
·
d
−
1
]
−
1
or [mg/L]
−
1
) for a certain contaminant
means a risk of 2 excess cancer incidences per 1000 persons with a lifetime expo-
sure to 1
kg
bw
−
1
([
μ
g
·
·
d
−
1
or at a concentration of 1 mg/L. This Unit risk can be
converted to a Critical Exposure value (Reference dose) once a decision is taken on
the acceptable excess cancer risk, as follows:
g/kg
bw
−
1
μ
·
Critical Exposure value
genotoxic carcinogens
=
excess cancer risk
/
Unit risk
(5.6)
The decision on the acceptable excess cancer risk is a policy decision. Values
used in Human Health Risk Assessment in regard to contaminated sites range world-
wide between 1 in 10
4
and1in10
6
. Therefore, it is clear that Critical Exposure
values for genotoxic carcinogens can easily vary by two orders of magnitude,
depending on national policy.
Several alternative approaches are commonly used. The Contaminated Land
Policy in UK, for example, uses the
Index Dose approach
for deriving Health
Criteria Values for non-threshold carcinogens (Environment Agency
2008
). This
Index Dose corresponds to the dose expected to be associated with a minimum
excess risk of cancer. It is calculated by applying a safety factor to the BMDL
10
(or T25) from animal experiments, or, if adequate human data are available, by using
the dose corresponding to an excess lifetime cancer risk of 1/100,000. The BMDL
10
corresponds to the lower 95% confidence interval of the benchmark exposure at a
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