that can take months to years to complete and
The guidance manual and all profiles are avail-
is often costly. Once properly validated, these
able on CD-ROM and on ATSDR's Web site
mathematical models can assist in exposure
at www.atsdr.cdc.gov . The first six profiles
assessments of toxic chemicals, aiding the
pertain to chemical mixtures found at NPL
investigator in identifying important routes of
hazardous waste sites. The last three profiles
exposure leading to observed high levels of the
deal with mixtures that are found at Department
chemicals in tissues of the population around
of Defense (DOD) and Department of Energy
sites.
(DOE) sites. The guidance manual and the
DOD/DOE profiles are also available as printed
For example, PBPK models were constructed
copies.
for 25 common PCB congeners for residents of
Anniston, Alabama, an area that has had a long-
Also during fiscal year 2002, ATSDR continued
standing fish advisory because of PCBs. The
its support of experimental research to enhance
models were used to investigate the contribution
the understanding of the underlying mecha-
of fish consumption to the observed high blood
nisms of toxicity following exposure to chem-
levels potentially associated with these PCBs in
ical mixtures. Scientists from ATSDR and
the community. Applying assumptions based on
scientific knowledge of the toxicity of PCBs and
Netherlands selected a chemical mixture and
habits of the population, the computer modeling
predicted its joint toxicity according to assess-
effort showed that approximately 80% of the
ment methods used to evaluate environmental
observed high blood levels in the population can
chemical mixtures. Following this process, a
be attributed to fish consumption.
carefully designed in vivo study with the 4-com-
ponent mixture was conducted. A report is being
In other situations, SAR methods are used to
prepared to summarize and compare the pre-
identify toxic risks for chemicals when experi-
dicted and observed joint toxicity of this mixture.
mental data are not available. For example, tox-
icity for 2-chloro-6-fluorophenol was examined
Computational Toxicology
upon a request by New York health officials
and a congressman from New York who wanted
Program
to provide information to his constituents. The
ATSDR's Substance-Specific Applied Research
phenol compound was released in a spill from
Program incorporates state-of-the-art computa-
a chemical facility to the surrounding environ-
tional toxicology methods to aid in interpreting
ment, and there was no known toxicity infor-
and assessing short, intermediate, and long-term
mation available on this chemical. ATSDR
health effects associated with exposure to
computational Toxicology Laboratory scien-
hazardous substances. These methods include
tists employed SAR methods to evaluate toxic
physiologically based pharmacokinetic/
endpoints, including mutagenicity, carcinoge-
pharmacodynamic (PBPK/PD) modeling, struc-
nicity, and developmental and dermal toxicity.
ture-activity-relationship (SAR) techniques, and
On the basis of the analysis, the chemical was
benchmark dose (BMD) models.
predicted to have little potential for toxicity.
However, 2-chloro-6-fluorophenol was pre-
PBPK/PD, BMD, and SAR are computer-based
dicted to cause skin sensitization, on the basis
mathematical models used to predict the action
of the available information from chemicals
of chemicals on the body in the absence of
with similar chemical structures. Thus, avoiding
adequate experimental data. The alternative
skin contact was recommended. The results and
to mathematical models is experimental work
38 chapter 2
Previous Page
