Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 525

frequency of exposure e.g., responses to acute exposures (a single exposure or mul-
tiple exposures occurring within twenty four hours or less) may be different from
those produced by sub-chronic and chronic exposures. Not all observed responses
within a study, irrespective of exposure duration or frequency, will represent toxicity
per se. They may encompass a range of effects from physiological through pharma-
cological and toxic manifestations. Although it sometimes may be difficult to make
a clear distinction between these responses, an attempt to do so should be made.
It is essential that all relevant toxicity end points (statistically and/or biologically
significant) be identified for consideration when evaluating data for the presence or
absence of non-toxic levels.
Physiological responses vary within limits which are in accord with the normal
functioning of a living organism; examples of such response are the usual respira-
tory and pulse rate increases associated with increased physical activity, systemic
changes associated with normal pregnancy, and those associated with homeostatic
mechanisms. These variable factors are not important toxicity end points in sub-
chronic and chronic exposure studies unless their fluctuations are abnormally altered
by a dose regimen. If such alterations occur at a particular dose or are part of a dose-
response relationship, they should be correlated with other toxicity end points which
maybepresent.
Pharmacological responses are altered physiological functions arising from inter-
action of a contaminant with a cellular receptor site, are reversible, and are usually of
limited duration following removal of the stimulus. Whilst some of these responses
may be undesirable under certain circumstances, they are distinguished from toxic
(adverse) responses by generally not causing injury.
Toxic responses may be reversible or irreversible, but are distinguished from
other types of responses by being injurious and therefore adverse and harmful to
living organisms or tissues. A contaminant which causes a physiological or pharma-
cological effect may produce a toxic response if the exposure is prolonged and/or if
the dose is increased beyond a certain level. The reversibility or otherwise of such
responses may also depend on these two factors. The reversibility or irreversibility
of a histopathological change will depend on the ability of the injured organ or tis-
sue to regenerate. For example, liver has a relatively great ability to regenerate and
many types of injury to this organ are reversible. By contrast, differentiated cells
of the central nervous system are not replaced and many injuries to the CNS are
irreversible.

12.3.3 Assessment of the Quality of the Data Characterising
the Hazard

The following considerations address the acceptability of experimental studies and
the documentation provided:

• The adequacy of the experimental design and other experimental parameters,

including: the appropriateness of the observational and experimental methods;