In its efforts to provide public health guidance to state and local health departments, other federal agencies, health professionals, and the public on the health effects of environmental pollutants, the Agency for Toxic Substances and Disease Registry (ATSDR) relies on the latest advances in computational toxicology. Housed within the Division of Toxicology and Environmental Medicine, the Computational Toxicology Laboratory (CompTox Lab) supports the agency mission by developing and applying state-of-the-art computational toxicology methods such as physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, quantitative structure-activity relationship (QSAR) methods, and benchmark dose (BMD) models. The developed PBPK, QSAR and BMD models are then implemented to determine and characterize risks from exposure to hazardous substances.
PBPK models mathematically describe
absorption, distribution, storage, metabolism, and excretion of
chemicals as they are
introduced
into the body. The models help predict human toxicity following
exposure to hazardous substances. The most common modeling applications
involve predictions based on information derived from animals (across
species extrapolations) or exposure routes (across route extrapolations)
other than those being studied.
The current CompTox Lab library of PBPK models includes the following chemicals:
QSAR techniques are used to estimate
the toxicity of poorly characterized substances based on comparisons to well-studied substances having similar chemical structures. TOPKAT, a commercially
available software, is used to predict toxicity endpoints based on chemical structure. The software predicts carcinogenicity in
male and female mice and rats, developmental toxicity, mutagenicity, log octanol/water partition coefficients, oral LD50s, and oral chronic
LOAELs in rats.
Benchmark dose (BMD) modeling is an
approach in which the dose response is modeled and the lower confidence
bound for a dose at a specified response level is calculated. BMD
is used to derive health guidance values by estimating the dose of a toxic substance without appreciable
risk or adverse health outcome. This is an alternative method to
the traditional threshold model approach (NOAEL/LOAEL) that is commonly
used for non-carcinogenic risk assessment of hazardous substances.
Emergency response and Bioterrorism
For more information, contact
Agency for Toxic Substances and Disease Registry
Division of Toxicology and Environmental Medicine
1600 Clifton Road NE, Mailstop F-32
Atlanta, GA 30333
Phone: 1-800-CDC-INFO • 888-232-6348 (TTY)
Email: cdcinfo@cdc.gov