Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 533

remembered in assessing a result as statistically significant. Conversely, a finding
that is not statistically significant may have biological significance when considered
in the light of the likely toxicological or pharmacological action of the contami-
nant, or when combined with results from other studies. Thus, evaluators should
note trends or transient changes in parameters if there is an indication that these
may be related to dosing with the contaminant in some way. This information
may be useful when comparing results across studies and in the consideration of
the overall significance or relevance of an observed effect, i.e., in one study an
effect may be only a trend whilst in another study it may be very clearly treatment-
related.
A difficult problem for evaluators is the fact that some studies producing either
clearly positive or negative results may have to be considered as flawed. In any long-
term study there may be questionable components of the study and an experienced
toxicologist must learn to recognise what is useful and reliable and discard what is
not. The use of a seriously flawed negative study may provide only a false sense
of security. On the other hand, a flawed positive study may be entitled to some
weight; how much is a matter of judgement (Task Force of Past Presidents 1982 ).
Data obtained from studies carried out many years ago should not be dismissed out-
of-hand simply because they do not meet today's standards; they may provide some
useful information. This is a matter for scientific interpretation and judgement on a
case-by-case basis.

12.3.5.13 Completion of Hazard Analysis

At this point the assessor should have formulated judgments and supporting
rationale concerning:

• the acceptability of the study and its database;

• the existence of biologically important adverse effects;

• the relevance of any factors noted during the evaluation which might have had

some bearing on the outcome of the study and modified the findings in some
way;

• the likelihood that any of the observed effects were induced by the administered

contaminant.

The evaluator should succinctly summarise the critical toxicokinetic and tox-
icological data, together with any modifying factors for the study under review.
The lowest, or most appropriate NOEL/NOAEL, or the absence thereof, should
be stated, with a clear indication of the effect(s) on which it was based (i.e.,
the lowest-observed effect level or LOEL should be apparent). It is important to
correlate findings seen in different studies; whilst this is done within the final sum-
mary of all toxicity studies, it will often be appropriate to make some mention of
cross-study correlations (or the unexpected/unexplained absence of them) within
individual study summaries. Possible or proven mechanisms of toxicity should also
be discussed and included in the summary.