Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 534

12.3.6 Evaluation of the Weight-of-Evidence and Consideration
of the Toxicology Database In Toto
The essential purpose of toxicity studies is the detection of valid biological evi-
dence of the hazard potential of the contaminant being investigated. In this chapter,
the evaluation of the weight of evidence 1 produced by toxicity studies is that pro-
cess which considers the cumulative data pertinent to arriving at a level of concern
about the potential adverse effects of a contaminant. It is composed of a series of
judgments concerning the adequacy, validity, and appropriateness of the methods
used to produce the data base, and those judgments which bring into causal, com-
plementary, parallel, or reciprocal relationships, all the data considered. Because our
knowledge about mechanisms of toxicity is still developing, because good epidemi-
ological evidence is seldom available, and because animal studies are not always
conclusive, the information available at a given time may provide only “persuasive”
rather than “hard” evidence of a defensible presumption, one way or the other, about
the potential health effects of a contaminant under given conditions of exposure.
Therefore, it is necessary to succinctly discuss the rationale for judgments and con-
clusions contained in Risk Assessments together with any associated uncertainties.
This becomes important when new data or new scientific knowledge requires re-
evaluation of the database or a change in a previous Risk Assessment or regulatory
action.
At present, there is no acceptable substitute for informed judgment, based on
sound scientific principles, in the analysis, evaluation, interpretation, and weighting
of biological and toxicological data derived from animal toxicity studies conducted
according to currently available protocols.
It is also accepted practice to apply safety or uncertainty factors to the
NOEL/NOAEL derived from animal studies when estimating an ADI (or TDI) as
an aid in evaluating the acceptability of actual or potential human exposures
In addition to identifying toxic effects and the doses at which these effects do
or do not occur, toxicity studies may yield insight into the mode- or mechanism of
action of a contaminant. The evaluator may be able to combine information from
a number of studies within the database (e.g., metabolic/toxicokinetic, acute, short-
term repeat-dose, subchronic, chronic/carcinogenicity, developmental, reproductive,
and genotoxicity studies), to adduce information about the mode or mechanism of
toxic action of the contaminant.
At the point of overviewing the entire toxicology database the WHO/IPCS
Conceptual Framework for Cancer Risk Assessment (Dybing 2002 , Boobis et al.
2006 ) can be applied. This “Framework” is an analytical tool providing a logi-
cal, structured approach to the assessment of the overall weight of evidence for a
1 “Strength of evidence” is commonly taken to mean the degree of conviction regarding the out-
come of an experiment e.g. The US National Toxicology Program's “clear evidence”, “some
evidence”, “equivocal evidence” and “no evidence” of carcinogenicity. “Weight of evidence”
involves integration of all available data, not just one study.