fluids (blood and urine, for example).
This method quantifies the amount of
a chemical that has been absorbed into
the body from all potential sources.
Biomonitoring data are discussed in
terms of biomarkers, which are commonly divided into three categories:
biomarkers of exposure, biomarkers of
effect and biomarkers of susceptibility. 9 But the collection of biomonitoring data—which involves selecting a
target population, identifying chemicals and biomarkers, collecting and
analyzing samples, and interpreting
the results—can be challenging.
Many population-based biomonitoring efforts are under way. For example,
a national survey conducted by the CDC
measures numerous chemicals and their
metabolites in a representative sample
of the U.S. population. The findings are
published periodically and represent one
of the largest publicly available biomonitoring datasets. 10
Biomonitoring data integrates exposures from multiple sources and pathways
to provide a direct measure of total exposure and is, therefore, a powerful tool
for assessing aggregate exposure and risk.
This data can be used to assess trends in
exposures over time, evaluate the effectiveness of exposure-reduction policies,
provide direction for future research and
help medical professionals diagnose people who have potentially been exposed
to excessive amounts of chemicals. Collecting and analyzing biomonitoring data
requires significant resources, so only a
limited number of people, compounds
and body fluids have been studied to
date. Also, these data provide no information on exposure conditions, such as frequency, duration, magnitude of exposures
or the exposure routes that contributed to
the total measured body burden.
REACH
The European Union’s Registration, Eval-
uation, Authorization and Restriction of
Chemicals (REACH) legislation requires
all chemicals manufactured, imported
and used in the EU to be assessed for
safety. Its underlying principle is that the
use of chemicals under “reasonably fore-
seeable conditions” should not adversely
affect human health and the environ-
ment. REACH places responsibility for
demonstrating the safety of chemicals
on industry. Companies must identify,
manage and communicate the risks that
chemicals may pose to human health
and the environment.
Risk Assessment’s New Era | FEATURE
are expected to establish separate DNELs
for different population groups (general
population, workers), exposure routes
(inhalation, dermal) and types of effects
(acute, chronic).
Although REACH requires safety assessments prior to the use of a chemical
in commerce, it may prove difficult to determine all foreseeable uses and exposure
scenarios. Relevant environmental monitoring data are often lacking. Available
exposure models are also based on limited
data and typically contain many conservative default values. In addition, DNELs
are not yet available for many substances,
population groups, exposure routes or effects, and the values derived using default
calculations often differ significantly
from health guidelines derived using a
weight-of-evidence approach. 12
Toxicity Testing in the 21st Century
The groundbreaking report “Toxicity
Testing in the 21st Century: A Vision
and a Strategy,” published in 2007 by
the National Research Council (NRC),
outlined how chemical health risks
should be evaluated in the future. 13 The
report proposed using advances in science and technology to assess chemical hazards and prioritize chemicals for
more in-depth toxicity testing.
NRC’s proposed toxicity testing system
would rely mainly on understanding toxicity pathways (that is, the cellular response
pathways that can result in adverse health
effects when sufficiently perturbed). Toxicity testing would shift from high-dose,
whole-animal testing to new rapid assays
and high-throughput techniques designed
to evaluate biologically significant alterations in exposed cells, tissues or organisms.
Targeted testing of some chemicals in animals would clarify and refine information
from toxicity pathway tests and ensure the
adequate evaluation of chemicals. Coupled
with other exposure and risk assessment
components, this information could enable
the translation of cellular tests to whole
human systems.
NRC’s proposed approach could make
toxicity testing quicker, less expensive
and more directly relevant to human exposure concentrations, which would help
industrial hygienists better explain how
