Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 556

• How good is the key study?

• Are the data from laboratory or field studies? Are the data for single species

or multiple species?

• If the hazard is carcinogenic, comment on issues such as: observation of sin-

gle or multiple tumour sites; occurrence of benign or malignant tumours;
certain tumour types not linked to carcinogenicity; use of the maximum
tolerated dose

• If the hazard is other than carcinogenic, what endpoints were observed, and

what is the basis for the critical effect?

•

What other studies support this finding

•

What valid studies conflict with this finding.

• What are the significant data gaps?

As many relevant studies as possible should be collated and rigorously
assessed as to their strengths and weaknesses to determine the key studies. This
is particularly important where quantitative risk estimates will be undertaken or
where there are apparently contradictory studies; in the latter case, the studies
that are considered to be adequate in their design and interpretation will need
to be appraised to determine the overall weight-of-evidence. See Section 2.6 for
further information on weight of evidence.
2. Besides the health effect observed in the key study, are there other health
endpoints of concern?
3. Consider available epidemiological or clinical data. For epidemiological studies:

• What types of studies were used, i.e., ecologic, case-control, cohort?

• Assess the degree to which exposures were adequately described.

• Assess the degree to which confounding factors were adequately

accounted for.

• Assess the degree to which other causal factors were excluded.

For further information refer to Section 3.4 “Assessing the relationship between
a possible cause and an outcome”.
4. How much is known about the biological mechanism by which the agent
produces adverse effects?

• Consider relevant studies on mechanisms of action which may include

metabolism studies.

•

Does this information aid in the interpretation of the toxicity data?

• What are the implications for potential health effects?

5. Consider any negative or equivocal findings in animals or humans, and whether
these data were considered in the Hazard Identification.
6. Consider the Hazard Identification and consider the significance of each of the
following.

• confidence in conclusions;

• alternative conclusions that are also supported by the data;