Current risk assessment
procedures are typically based on overall daily exposure levels,
and tend to emphasize effects resulting from continuous exposures
over a lifetime. This basis is widely recognized to be an oversimplification.
There has been an increasing realization that exposures are more
likely to be experienced as episodes (i.e., bursts or spikes,
or intermittent exposures) of varying levels. As scientists delve
further into the subject, they are discovering that Haber's Law
(i.e., concentration multiplied by duration) does not properly
explain the relationship between exposure/dose and an effect.
of exposure effects on toxic responses require consideration
of the entire exposure profile, including the timing, duration,
and intermittent nature of exposures reflecting realistic scenarios
encountered in practical settings. The proper metric for exposure
may be highly dependent on the pharmacokinetic properties of
the chemical or exposure in question. The toxic effects considered
in models must be carefully chosen to reflect the sensitive endpoints
based on the exposure characteristics.
Models have been
developed over the last decade which begin to address the effect
of duration of exposure in addition to exposure levels; however,
most of these models do not incorporate mechanistic information.
In addition, only limited work has been done on developing efficient
designs for studying dose-rate effects, and these designs tend
to be simplistic.
Under the sponsorship
of EPA and others, at an August 1998 workshop in DC, participants
discussed how exposure-duration and toxicity relationships are
or can be incorporated into the risk assessment process for less-than-lifetime
exposures. Dr. Lefohn, A.S.L. & Associates, was invited to
participate in the workshop and provide one of the short presentations.
The workshop participants discussed
During the meeting,
several presentations were made to provide specific examples
of the various issues. The remainder of the meeting was organized
around breakout sessions that discussed where current risk assessment
approaches could be improved.
Much of the current
risk assessment methodology is based on Haber's Law (i.e., C
x T). A very important conclusion reached by one of the working
If C x T, pure and simple, does not
work (it is not appropriate), then resulting risk assessments
become more problematic. Current default methods often assume
a simple C x T relationship. The inappropriateness of this assumption
can result in both overestimates and underestimates of risk,
with the latter being more likely when extrapolation is toward
periods of shorter duration....
As a result of the
workshop, the EPA published the report "Summary of the
U.S. EPA Workshop on the Relationship between Exposure Duration
and Toxicity" in September 1998, which summarizes the
recommendations of the panel. Copies of the report can be obtained
U.S. Environmental Protection Agency
Risk Assessment Forum
401 M Street SW
Washington, DC 20460