for those chemical mixtures found at hazardous
cancer. The toxic endpoints evaluated included
waste sites on the NPL but also those mixtures
mutagenicity, carcinogenicity, and developmen-
that are found at Department of Defense (DOD)
tal toxicity. These chemicals were tetrachlo-
and Department of Energy (DOE) sites.
rophthalic acid, tetrachlorophthalic anhydride,
chlorendic anhydride, chlorendic acid, o-chloro-
Also during fiscal year 2001, ATSDR continued
styrene, m-chlorostyrene, p-chlorostyrene, alpha
its support of experimental research to enhance
beta dichlorostyrene, bis (4-chlorophenyl)
the understanding of the underlying mecha-
sulfone, triallyl isocyanurate, 1,2-diphenyl-
nisms of toxicity following exposure to chem-
hydrazine diphenylamine,
ical mixtures. Scientists from ATSDR and
N-ethyl-p-toluenesulfonamide, N-methyl-p-
toluenesulfonamide, and styrene-acrylonitrile
Netherlands, selected a chemical mixture and
dimer. Data analysis showed that 9 of the 15
predicted its toxicity based on assessment meth-
chemicals have a potential for carcinogenicity,
ods used to evaluate environmental chemical
6 have potential for developmental toxicity, and
mixtures. Following this, a carefully designed in
6 have a potential to cause mutagenicity.
vivo study with the 4-component mixture was
completed. The results are being analyzed and
Other activities of the Computational
will be compared with the predicted results to
Toxicology Program in fiscal year 2001 include
evaluate the accuracy of the predicted toxicity.
the following:
Interaction PBPK models were developed to
Computational
evaluate the joint toxicity of carbon tetrachlo-
Toxicology Program
ride, tetrachloroethylene, and trichloroethyl-
ene.
ATSDR's Substance-Specific Applied Research
Child-based PBPK models were constructed
Program incorporates state-of-the-art computa-
for tetrachloroethylene to help in the assess-
tional toxicology methods to aid in interpreting
ment of risk to children who live close to a
and assessing short, intermediate, and long-term
hazardous waste site.
health effects associated with exposure to
hazardous substances. These methods include
Great Lakes Human Health
physiologically based pharmacokinetic/
Effects Research Program
pharmacodynamic (PBPK/PD) modeling, struc-
ture-activity-relationship (SAR) techniques, and
The Great Lakes Human Health Effects
benchmark dose (BMD) models. PBPK/PD,
Research Program is intended to build on, and
BMD, and SAR are computer-based mathemati-
amplify, the results of past and ongoing
cal models used to predict the action of chemi-
fish-consumption research in the Great Lakes
cals on the body in the absence of adequate
basin, using existing structures and institutions
experimental data. The alternative to mathemati-
already involved in human health research.
cal models is experimental work that can take
This ATSDR-supported research program stud-
months to years to complete and is often costly.
ies known at-risk populations to further define
the human health consequences of exposure
For example, SAR was used to evaluate a
series of unusual chemicals identified by the
Great Lakes basin.
New Jersey Department of Health and Senior
Services in drinking water in Dover Township,
an area that had a high incidence of childhood
chapter 2 39
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