Comparing Exposure to Relevant Hazard
Information
This step involves an comparison
of the results of the exposure evaluation to the relevant
hazards data for a given exposure scenario. This process
normally takes into account the frequency and duration of
different exposure scenarios (e.g., is exposure considered
to be acute, sub-chronic or chronic?), and the route of
exposure (e.g., dermal, inhalation, oral), in order to identify
the appropriate hazards studies. Comparisons may include
either a qualitative discussion of hazard thresholds, relative
to exposures, or quantitative comparions. While there are
several approaches to a quantitative comparison, most involve
some estimate of the ratio between the results of hazard
studies, and the predicted level of exposure. This ratio
is used as a surrogate for the likelihood that a chemical
could cause harm under the specified exposure scenario(s).
Where risk assessors choose to develop quantitative assessments
for non-cancer endpoints, they typically select one of two
basic approaches:
(1) calculating a "Margin of Exposure,"
or
(2) calculating a "Margin of Safety."
These are described in the Explanatory
Notes for the ACA Human Exposure Framework (Item 18). The
choice of which approach to use, or whether another alternative
is more appropriate, is naturally up to an individual sponsor,
in consultation with risk assessors, regulatory and compliance
staff, risk managers and others.
The comparison of both hazard and exposure
data, either qualitatively or quantitatively, is an important
means of putting the potential effects of chemicals for
human health and the environment into context. Neither hazards
data nor exposure data alone are normally sufficient. In
general, a weight-of-evidence approach is normally used,
taking into account the severity of effects, dose response,
precision and accuracy of data, reliability, statistical
significance, biological relevance of the hazards, etc…
This last factor may be especially important. For example,
in carcinogenicity studies, adverse findings may be due
to genetic harm by the test chemical; or they may be a consequence
of the very high doses that are often used in long-term
animal studies, which can lead to physiological responses
that indirectly cause cancer, but that are not biologically
relevant under normal exposure conditions to humans.
